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Veröffentlichungen im Juni 2009

Auch zum Beginn des Sommers steht die Chitin und Chitosanforschung nicht in still. Weitere 130 Artikel wurden in Fachzeitschriften plaziert. Unter anderem kamen 50 Artikel aus China, 10 aus den USA und 9 aus Südkorea. Wollen Sie die Themenschwerpunkte erfahren?

Tags: chitosan, abstracts, knochenersatz, Chitosan-Nanopartikel

15 Artikel konzentrieren sich auf das Thema des Knochenersatzes. 33 veröffentlichen Neuigkeiten aus der Welt der Chitosan-Nanopartikel.

Hier die wichtigsten Keywords:

chitosan/hydroxyapatite membrane; nano-hydroxyapatite/chitosan cement; chitosan scaffolds; bone marrow stromal cell, critical size effects, Coating, chitosan-silicate hydrogel, carboxymethyl chitosan, chitosan gel sponge, chitosan/collagen scaffolds, collagen-chitosan-hydroxyapatite, superporous hydrogel; collagen-chitosan-hydroxyapatite nanocomposites, light-curable chitosans

 1: Preparation of chitosan/hydroxyapatite membrane and its effect on cell culture

Yang, Julin; et al; Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2009 Jun26(3):580-4

Extract: Compound membranes of chitosan/hydroxyapatite were prepared by blending. The physical performance showed that the air-water contact angles decreased from chitosan's 103 degrees to chitosan/hydroxyapatite's 57 and the water adsorption rate increased slightly. When immersed into culture medium, the materials adsorbed Ca2+, and low crystalline hydroxyapatite deposited on the surface of the membranes. Chitosan/hydroxyapatite compound membranes could enhance the attachment and proliferation of mescenchymal stem cells (MSCs). After 12 days' induction on the materials, the alkaline phosphatase (ALP) activity value of MSCs on the compound membrane was 10.1, being much higher than 1.6 on chitosan membrane (P<0.01). All these results indicate that chitosan does not have very good affinity for MSCs, but the biocompatibility of chitosan can be apparently enhanced after mixing with hydroxyapatite. The compound membrane stimulates MSCs to differentiate into osteoblasts and it may be a good potential material for bone substitution.

PMID: 19634677 [found with GoPubMed]

 2: Chondrogenesis on BMP-6 loaded chitosan scaffolds in stationary and dynamic cultures

Tığlı, R S; et al; Biotechnol Bioeng 2009 Jun

We originally investigated the suitability of chitosan scaffolds loaded with bone morphogenetic protein 6 (BMP-6) in both stationary and dynamic conditions for cartilage tissue engineering. In the first part of the present study, ATDC5 murine chondrogenic cells were seeded in chitosan and BMP-6 loaded chitosan scaffolds and cultured for 28 days under static conditions. In the following part, we examined the influence of dynamic cultivation conditions over BMP-6 loaded chitosan scaffolds by using rotating bioreactor with perfusion (RCMW). Tissue engineered constructs were characterized by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) assay, scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) and biochemical assays for glycosaminoglycans (GAG) deoxyribonucleic acid (DNA) and collagen Type II quantification. At the end of 4 weeks static incubation period high levels of GAG (21.22 mg/g dry weight), DNA amounts (1.37 mg/g dry weight) and collagen Type II amounts (1.94 microg/g dry weight) were achieved for BMP-6 loaded chitosan scaffolds compared to chitosan scaffolds. However, the results obtained from morphological observations suggested hypertrophic differentiation of ATDC5 cells in the presence of BMP-6 under stationary conditions. The influence of mechanical stimulation appeared significantly with differentiated cells, cultured under dynamic conditions, showing the effect of retaining their phenotypes without hypertrophy. Biotechnol. Bioeng. (c) 2009 Wiley Periodicals, Inc.

PMID: 19575410 [found with GoPubMed]

 3: In vitro and in vivo evaluation on the bioactivity of ZnO containing nano-hydroxyapatite/chitosan cement

Li, Z; et al; J Biomed Mater Res A 2009 Jun

A ZnO containing nano-hydroxyapatite/chitosan (n-HA/CS) cement was developed and its bone formation ability was investigated in vitro and in vivo. The physico-chemical properties of the cement were determined in terms of pH variation during and after setting, injectability and wettability. The results indicated that, the pH varied from 7.04 to 7.12 throughout the soaking of the cement in distilled water. The injectability was excellent during the first 4 min, but the cement became less injectable or even not injectable at all after 7 min setting. The static contact angle of the cement against water was 53.5 +/- 2.7 degrees . The results of immersion tests in simulated body fluid (SBF) indicated that the cement exhibited excellent bone-like apatite forming ability. In vivo studies, involving the installation of the cement of tibial-bone defects in rabbit tibia revealed an inflammatory response around the cement at 3 days of implantation. After 4 weeks, the inflammation began to disappear and the cement had bound to the surrounding host bone. Radiological examination also confirmed that the ZnO containing n-HA/CS cement significantly induced new bone formation. These results suggest that the ZnO containing n-HA/CS cement may be beneficial to enhance bone regeneration in osseous defect sites. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2009.

PMID: 19562749 [found with GoPubMed]

 4: Effect of chitosan particles and dexamethasone on human bone marrow stromal cell osteogenesis and angiogenic factor secretion

Guzmán-Morales, J; et al; Bone 2009 Jun

Chitosan is a polysaccharide scaffold used to enhance cartilage repair during treatments involving bone marrow stimulation, and it is reported to increase angiogenesis and osteogenesis in vivo. Here, we tested the hypotheses that addition of chitosan particles to the media of human bone marrow stromal cell (BMSC) cultures stimulates osteogenesis by promoting osteoblastic differentiation and by favoring the release of angiogenic factors in vitro. Confluent BMSCs were cultured for 3 weeks with 16% fetal bovine serum, ascorbate-2-phosphate and disodium beta-glycerol phosphate, in the absence or presence of dexamethasone, an anti-inflammatory glucocorticoid commonly used as an inducer of BMSC osteoblast differentiation in vitro. As expected, dexamethasone slowed cell division, stimulated alkaline phosphatase activity and enhanced matrix mineralization. Added chitosan particles accumulated intra- and extracellularly and, while not affecting most osteogenic features, they inhibited osteocalcin release to the media at day 14 and interfered with mineralized matrix deposition. Interestingly, dexamethasone promoted cell attachment and suppressed the release and activation of matrix metalloprotease-2 (MMP-2). While chitosan particles had no effect on the release of angiogenic factors, dexamethasone significantly inhibited (p
PMID: 19540373 [found with GoPubMed]

 5: Histological evaluation of chitosan-based biomaterials used for the correction of critical size defects in rat's calvaria

Spin-Neto, R; et al; J Biomed Mater Res A 2009 Jun

Chitosan, a biopolymer obtained from chitin, and its derivates, such as chitosan hydrochloride, has been reported as wound healing accelerators and as possible bone substitutes for tissue engineering, and therefore these substances could be relevant in dentistry and periodontology. The purpose of this investigation was to make a histological evaluation of chitosan and chitosan hydrochloride biomaterials (gels) used in the correction of critical size bone defects made in rat's calvaria. Bone defects of 8 mm in diameter were surgically created in the calvaria of 50 Holtzman (Rattus norvegicus) rats and filled with blood clot (control), low molecular weight chitosan, high molecular weight chitosan, low molecular weight chitosan hydrochloride, and high molecular weight chitosan hydrochloride, numbering 10 animals, divided into two experimental periods (15 and 60 days), for each biomaterial. The histological evaluation was made based on the morphology of the new-formed tissues in defect's region, and the results indicated that there was no statistical difference between the groups when the new bone formation in the entire defect's area were compared (p > 0.05) and, except in the control groups, assorted degrees of inflammation could be seen. In conclusion, chitosan and chitosan hydrochloride biomaterials used in this study were not able to promote new bone formation in critical size defects made in rat's calvaria. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2009.

PMID: 19536827 [found with GoPubMed]

 6: Bioactive Coating of Silica Xerogel/Chitosan Hybrid on Titanium by a Room-Temperature Sol-Gel Process

Jun, S H; et al; Acta Biomater 2009 Jun

A bioactive coating consisting of a silica xerogel/chitosan hybrid was made on Ti at room-temperature as a novel surface treatment for metallic implants. A crack-free thin layer (< 2 mum) was coated on Ti with a chitosan content of more than 30 % by volume through a sol-gel process. The coating layer became more hydrophilic with increasing silica xerogel content, as assessed by the contact angle measurement. The hybrid coatings afforded excellent bone bioactivity by inducing the rapid precipitation of apatite on their surface when immersed in a simulated body fluid (SBF). Osteoblastic cells cultured on the hybrid coatings were more viable than those on the pure chitosan coating. Furthermore, the alkaline phosphate (ALP) activity of the cells was significantly higher on the hybrid coatings than on the pure chitosan coating, and the highest level was achieved on the hybrid coating containing 30 % chitosan. These results indicated that the silica xerogel/chitosan hybrids are potentially useful as room-temperature bioactive coating materials on titanium-based medical implants.

PMID: 19531388 [found with GoPubMed]

 7: Synthesis and characterization of chitosan-silicate hydrogel as resorbable vehicle for bonelike-bone graft

Shirosaki, Yuki; et al; J Nanosci Nanotechnol 2009 Jun9(6):3714-9

The use of bone grafts is required to restore skeletal integrity and enhance bone healing of large defects in several areas of regenerative medicine, such as: orthopedic and maxillofacial procedures. Some of these bone grafts can be resorbed in a time controlled way, in order to allow the correct process of natural re-construction of the involved bone tissue to occur. The Bonelike graft is a bone substitute that mimics the inorganic composition of bone; this biomaterial was developed and characterized over the last decade. In a granular form, Bonelike has proved its highly bioactive behavior in medical applications, such as; maxillofacial and orthopedics surgery. The clinical applications in maxillary bone defects indicated a good bone bonding between new formed bone and the Bonelike granules. The purpose of this study was to develop a new injectable system for the application of Bonelike using a resorbable vehicle which may be used in minimal invasive surgery. A new hydrogel derived from chitosan and y-glycidoxypropyltrimethoxysilane (GPTMS) was synthesized and characterized. The mixture derived from chitosan and GPTMS existed in sol state at room temperature and formed a hydrogel at 37 degrees C. The degradability of the hydrogel could be controlled by the concentration of chitosan and GPTMS, and the presence the presence of Bonelike did not affect its degradability. The pH changes caused by the degradation of this hydrogel were small, so it is not expected to cause any deleterious effect in vivo conditions.

PMID: 19504908 [found with GoPubMed]

8: Bone morphogenetic proteins in cranial reconstructions: clinical evaluation of heparin-chitosan as a carrier for BMP-2

Docherty Skogh, Ann-Charlott et al; Plast Reconstr Surg 2009 Jun123(6):192e-3e
PMID: 19483536 [found with GoPubMed]

 9: Cytotoxicity and genotoxicity of superporous hydrogel containing interpenetrating polymer networks

Yin, Lichen; et al; Food Chem Toxicol 2009 Jun47(6):1139-45

The superporous hydrogel containing poly(acrylic acid-co-acrylamide)/O-carboxymethyl chitosan (O-CMC) interpenetrating polymer networks (SPH-IPN) that had been developed as an oral delivery vehicle for protein drugs was subject to cytotoxicity and genotoxicity testing, thus evaluating its biological safety in use. In a battery of cytotoxicity assays on RBL-2H3 and Caco-2 cells, the SPH-IPN caused minimal damage towards cell viability, lysosomal activity, and metabolic activity following both direct and indirect treatment. The SPH-IPN did not induce cell apoptosis or DNA breakage in the above cell lines; it did not increase micronucleus (MN) incidence in mouse bone marrow, either. Therefore, the SPH-IPN was preliminarily considered to be biocompatible and might be a safe carrier for protein drugs. In addition, using the HPLC method, residual acrylic acid, acrylamide, and glutaraldehyde in the SPH-IPN were quantified to be 1.4, 2.0, and below 0.2 ppm, respectively. Lack of these low molecular monomers and crosslinker that were mainly responsible for the toxicity provided evidence for the good biocompatibility of the SPH-IPN.

PMID: 19425232 [found with GoPubMed]

 10: Surface functionalization of titanium with carboxymethyl chitosan and immobilized bone morphogenetic protein-2 for enhanced osseointegration

Shi, Zhilong; et al; Biomacromolecules 2009 Jun10(6):1603-11

Orthopedic implant failure has been attributed mainly to loosening of the implant from host bone, which may be due to poor bonding of the implant material to bone tissue, as well as to bacterial infection. One promising strategy to enhance tissue integration is to develop a selective biointeractive surface that simultaneously enhances bone cell function while decreasing bacterial adhesion. In this in vitro study, the surfaces of titanium alloy substrates were functionalized by first covalently grafting carboxymethyl chitosan (CMCS), followed by the conjugation of bone morphogenetic protein-2 (BMP-2) to the CMCS-grafted surface. Bacterial adhesion on the substrates was assayed with Staphylococcus aureus and Staphylococcus epidermidis . Cell functions were investigated using osteoblasts and human bone marrow-derived mesenchymal stem cells. The results showed that bacterial adhesion on both the CMCS and CMCS-BMP-2 functionalized surfaces was significantly reduced compared to that on the pristine substrates. In addition, the CMCS-BMP-2 modified substrates significantly promoted attachment, alkaline phosphatase activity, and calcium mineral deposition of both osteoblast and human bone marrow-derived mesenchymal stem cells. The achievement of the dual functions of bacterial adhesion reduction and cell function promotion by the CMCS-BMP-2 modified titanium substrates illustrates the good potential of such surfaces for enhancement of tissue integration and implant longevity.

PMID: 19391583 [found with GoPubMed]

 11: Peripheral nerve regeneration by transplantation of BMSC-derived Schwann cells as chitosan gel sponge scaffolds

Ishikawa, Namiko; et al; J Biomed Mater Res A 2009 Jun89(4):1118-24

It is said that bone marrow stromal cells (BMSCs) are able to differentiate into different kinds of cells, including Schwann cells, under relevant conditions (Dezawa et al., Eur J Neurosci 2001;14:1771-1776). In the previous paper, we demonstrated that chitosan gel sponge is one of the effective scaffolds for regenerating axons of the rat sciatic nerve (Ishikawa et al., J Biomed Mater Res A 2007;83:33-40). In the present study, we examined whether BMSC-derived Schwann cells with chitosan gel sponges were one of the effective scaffolds for peripheral nerve regeneration in rats. BMSC-derived cells with Schwann cell characteristics were labeled by green fluorescent protein using a retrovirus. An 8-mm gap was made by removing a nerve segment from the rat peripheral nerve, and chitosan gel sponges containing BMSC-derived Schwann cells were grafted, sandwiching the proximal and distal stumps of the transected nerve. Rats were sacrificed at 7, 14, and 28 days, and 2 and 4 months after transplantation. Immunohistochemistry demonstrated that regenerating axons were found near transplanted Schwann cells 7 days after surgery and extended into the host distal nerve segment at 14 days after surgery. Electron microscopy showed that transplanted Schwann cells formed myelin sheaths on regenerating axons 1 month after transplantation. The mean diameter of myelinated fibers was increased from 2.58 mum at 2 months to 2.84 mum at 4 months postsurgery. This study indicates that chitosan gel sponges containing BMSC-derived Schwann cells have strong potentiality as a graft that can be used for peripheral nerve regeneration.

PMID: 19343770 [found with GoPubMed]

 12: The synergetic bone-forming effects of combinations of growth factors expressed by adenovirus vectors on chitosan/collagen scaffolds

Zhang, Yufeng; et al; J Control Release 2009 Jun136(3):172-8

Supporting and enhancing the regeneration and stability of alveolar bone at dental implant sites is necessary to improve implant integration and stability. In this study chitosan/collagen scaffolds combined with adenoviruses expressing either bone morphogenetic protein 7 (BMP-7), platelet-derived growth factor B (PDGF-B), or a combination of both BMP-7 and PDGF-B, were prepared by a freeze-drying method. The cytotoxicity of the resulting biomaterials, and their potential effects on cell proliferation and differentiation towards an osteoblast phenotype, were studied in an initial in vitro study using human periodontal ligament cells (HPLCs). These in vitro results indicate that the scaffold materials are not cytotoxic, and moreover that scaffolds expressing PDGF-B show a higher proliferation rate, while scaffolds expressing BMP-7 show a stronger differentiation towards the osteoblast phenotype. In a subsequent in vivo study, scaffolds were implanted into surgically induced defects on both sides of the dog mandible. Bone formation, which was evaluated histomorphometrically at 4 and 8 weeks and after sacrificing the animals at 12 weeks, revealed a significant increase in bone formation in scaffolds expressing only BMP-7 and also the combined growth factors, with the highest increase occurring for the scaffold expressing both BMP-7 and PDGF-B. This study demonstrates the promising potential of biomaterial expression of combinations of growth factors such as BMP-7 and PDGF-B for bone regeneration in tissue engineering applications.

PMID: 19250951 [found with GoPubMed]

 13:Antibiotic delivery system using nano-hydroxyapatite/chitosan bone cement consisting of berberine

Zou, Qin; et al;. J Biomed Mater Res A 2009 Jun89(4):1108-17

Different concentrations of berberine were mixed with nano-hydroxyapatite/chitosan (n-HA/CS) bone cement to generate an antibiotic drug delivery system for treatment of bone defects. Properties of the system such as setting time, compressive strength, surface morphology, phase compositions, drug release profiles and antimicrobial activity were also characterized. It was shown that the setting time of the cement ranged from 17.03 +/- 0.50 min to 28.47 +/- 0.96 min and the compressive strength changed from 184.00 +/- 7.94 MPa to 120.33 +/- 9.02 MPa with the increase of berberine. The XRD, IR, and SEM analyses suggested that berberine powders were stable in the bone cement in simulated body fluid (SBF). In vitro release of berberine from the bioactive bone cement pellets in SBF could last more than 4 weeks. The release profiles of 1.0 wt % berberine loaded bone cement followed the Higuchi equation at the infusion stage. The drug loaded pellets can inhibit bacterial growth (Staphylococcus aureus) at the standardized berberine minimum inhibitory concentration of 0.02 mg/mL during berberine release from 1 to 28 days. The n-HA/CS bone cement only with 1.0 wt % berberine proved to be an efficient antibiotic drug delivery system.

PMID: 18767062 [found with GoPubMed]

 14: Synthesis and evaluation of collagen-chitosan-hydroxyapatite nanocomposites for bone grafting

Wang, Xiaoliang; et al; J; Biomed Mater Res A 2009 Jun89(4):1079-87

Incorporation of hydroxyapatite (HA) into the matrix of collagen (Col) and chitosan (Chi) by in situ synthesis was introduced to prepare nanocomposites. Structural investigations of the pure Col-Chi mixture validated the influence of Chi on Col assembly, but the molecular interactions between Col and Chi was partially depressed during the intervention of in situ HA synthesis, as revealed by FTIR and DSC analyses. A series of Col-Chi-HA (CCHA) nanocomposites with varying HA content were thereby prepared by a sequential method, involving in situ synthesis in the Col-Chi system, then gelling at 25 degrees C and subsequently washing the resultant elastic gel followed by dehydration consolidation. The structural characteristics and biological properties of the dehydrated CCHA nanocomposites were further evaluated by using XRD, FTIR, TG, and SEM analyses and the osteoblast culture experiment. Formation of a well integrated microstructure of organic fibers (ca. 90 nm in size) and dense matrix including inorganic aggregates (less than 30 nm in size) was found in these nanocomposites. Rat Ros 17/2.8 Osteoblasts proliferated and attached well on the surface of both CCHA nanocomposite and Col-Chi mixture. These results indicated that in situ HA synthesis in the Col-Chi system provided a feasible route for bone grafting nanocomposites.

PMID: 18478560 [found with GoPubMed]

 15: Chemically modified light-curable chitosans with enhanced potential for bone tissue repair

Qiu, Yongzhi; et al; J Biomed Mater Res A 2009 Jun89(3):772-9

Light curable polymers are showing great potential in overcoming some of the current obstacles in bone repair. With stereolithography, they can be fabricated into scaffolds with desired topography for repairing bone defects in irregular shapes. In this study, we developed a series of light curable chitosans, which have photocurability and good solubility in organic solvent. Through adjusting the feeding ratio of the raw components, the content of photocurable groups in the backbone of chitosan can be controlled. The light curable chitosans were characterized through FTIR-ATR and (1)H NMR, which also confirmed their controllable photocurability. NIH 3T3 fibroblasts were co-cultured with the photocured samples for 7 days and the results indicated that these photocured chitosans are cyto-compatible. Scaffolds with interconnected pores, fabricated using salt leaching and photocuring and seeded with fetal bovine osteoblasts, were implanted subcutaneously in the backs of athymic rat. Histological study on the implants at 6 weeks showed that the photocured chitosans have good osteoconductivity. The results indicated the light curable chitosans have good biocompatibility and osteoconductivity.

PMID: 18465814 [found with GoPubMed]


1: J Colloid Interface Sci 2009 Jun:

Study on the interaction between CdSe quantum dots and chitosan by scattering spectra.

Peng, J; Liu, S; Wang, L; Liu, Z; He, Y

Key Laboratory on Luminescence and Real-time Analysis, Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Beibei, Chongqing 400715, PR China.

Two different stabilizing agents thioglycolic acid (TGA) and l-cysteine (l-Cys) capped CdSe QDs with the diameter of 2nm were synthesized, large amounts of stabilizing agents connected to CdSe QDs surface through Cd-S bond. The interaction between chitosan and QDs had been investigated, respectively. The interaction lead to the remarkable enhancement of RRS, RNLS and the enchantments were in proportional to the concentration of chitosan in a certain range. Under the optimal conditions, compared with TGA-CdSe QDs, the interaction between l-Cys-CdSe QDs with chitosan owned more broad linear range 0.042-3.0mugmL(-1) and lower detect limits 1.2ngmL(-1). The influences of factors on the interaction between chitosan with QDs and some foreign substances were all examined, which showed that the methods had a good sensitivity and selectivity. Based on this, it is hoped to build a method for the determination of chitosan using CdSe QDs as probes. Through Fourier transform infrared spectroscopy (FTIR) transmission electron microscopy (TEM), it was speculated that CdSe QDs interacted with chitosan to form a network structure aggregates through electrostatic attraction and hydrophobic forces. The reasons for the enhancement of RRS intensity were assumed as follows: resonance enhanced Rayleigh scattering effect, increase of the molecular volume, and hydrophobic effect.

PMID: 19631331 [found with GoPubMed]

2: J Control Release 2009 Jun:

Preparation and characterization of chitosan/polyguluronate nanoparticles for siRNA delivery.

Lee, D W; Yun, K S; Ban, H S; Choe, W; Lee, S K; Lee, K Y

Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Korea.

Small interfering RNA (siRNA) has been widely investigated as a potential therapeutic for treatment of various diseases. However, the use of siRNA is limited due to its rapid degradation and low intracellular association in vitro and in vivo. Chitosan nanoparticles encapsulating siRNA were prepared using a coacervation method in the presence of polyguluronate (PG), which is isolated from alginate and is strongly related to ionic interactions of negatively charged alginate. Various physicochemical properties of chitosan/PG nanoparticles, including size, surface charge, morphology, and interaction with siRNA, were characterized. The mean diameter of siRNA-loaded chitosan-based nanoparticles ranged from 110 to 430 nm, depending on the weight ratio between chitosan and siRNA. Nanoparticles showed low cytotoxicity and were useful in delivering siRNA to HEK 293FT and HeLa cells. Chitosan/PG nanoparticles were considered promising for siRNA delivery due to their low cytotoxicity and ability to transport siRNA into cells, which can effectively inhibit induction of targeting mRNA.

PMID: 19567259 [found with GoPubMed]

3: J Microencapsul 2009 Jun:

Chitosan derivative nanocarrier: Safety evaluation, antibacterial property and ascorbyl palmitate encapsulation.

Wittayasuporn, M; Rengpipat, S; Palaga, T; Asawanonda, P; Anumansirikul, N; Wanichwecharungruang, S P

Program in Biotechnology, Faculty of Science.

A chitosan derivative, methyl ether-terminated poly(ethylene oxide)-4-methoxycinnamolyphthaloylchitosan (PCPLC) was prepared, characterized and self-assembled into nanoparticles. Encapsulation of ascorbyl palmitate (AP) into PCPLC gave 689 +/- 0.98 nm particles with encapsulation efficiency of 84% at 56% drug loading. The encapsulated AP showed significant improved stability as examined by (1)H NMR spectroscopy. The obtained particles displayed no short-term cytotoxicity against the human skin melanoma A-375 cell line using the MTT assay and no short-term skin irritation on human volunteers using a single topical application as patch and photopatch tests. In addition, aqueous suspension of PCPLC nanoparticles successfully inhibited the growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923.

PMID: 19566395 [found with GoPubMed]

4: Drug Dev Ind Pharm 2009 Jun:

Preparation and evaluation of N-caproyl chitosan nanoparticles surface modified with glycyrrhizin for hepatocyte targeting.

Lin, A; Chen, J; Liu, Y; Deng, S; Wu, Z; Huang, Y; Ping, Q

Pharmaceutics Laboratory of TCM, The Second Faculty of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China.

Background: The development of an efficient targeted drug delivery system into cells is an important subject for the advancement of drug carriers. In this study, a novel hepatocyte-targeted delivery system with glycyrrhizin (GL) surface modification based on N-caproyl chitosan (CCS) has been developed. Method: CCS was synthesized by acylation of amino group of chitosan, and GL was oxidized to be conjugated to the surface of N-caproyl chitosan nanoparticles (CCS-NPs-GL). The synthesized nanoparticles were first characterized for their morphology, particle size, zeta potential, in vitro stability in plasma, tissue distribution, and hepatocyte-targeting uptake in vivo. Results: The obtained results showed that the spherical and discrete nanoparticles prepared with oxidized GL/CCS ratio of 0.14:1 (w/w) exhibited a positive electrical charge and associated adriamycin quite efficiently (association efficiency: 87.5%). The prepared nanoparticles also possessed dimensional and GL surface-binding stability and slow release property in plasma in vitro. The biodistribution of these particles after intravenous injections in mice revealed accumulating drug concentrations in the liver, spleen, and lungs while decreasing drug concentrations in the heart and kidney. The content of adriamycin-loaded CCS-NPs-GL in the liver was 1.6 times higher than that of non-GL-modified CCS-NPs. Furthermore, in vivo uptake of CCS-NPs-GL by rat hepatocytes showed 2.1 times higher nanoparticle uptake compared with non-GL-modified CCS-NPs, which suggested that CCS-NPs-GL were preferentially distributed in hepatocytes by a ligand-receptor interaction. Conclusion: This article indicated that CCS-NPs-GL was a stable and effective drug delivery vehicle for hepatocyte targeting.

PMID: 19566386 [found with GoPubMed]

5: Biotechnol Prog 2009 Jun:

Biocompatible nanoparticles trigger rapid bacteria clustering.

Larsen, M U; Seward, M; Tripathi, A; Shapley, N C

Dept. of Chemical Engineering, Columbia University, New York, NY 10027.

This study reveals an exciting phenomenon of stimulated bacteria clustering. Rapid aggregation and microbial arrest are shown to occur in Escherichia coli solutions of neutral pH when chitosan nanoparticles with positive zeta potential are added. Because chitosan nanoparticles can easily be dispersed in aqueous buffers, the rapid clustering phenomenon requires only minuscule nanoparticle concentrations and will be critical in developing new methods for extricating bacterial pathogens. This work establishes the dominant role of electrostatic attraction in bacteria-nanoparticle interactions by varying the nanoparticle zeta potential from highly positive to strongly negative values, and by exploring concentration effects. For strongly negative nanoparticles, no clusters form, while aggregates are small and loose at intermediate conditions. In addition, optical density measurements indicate that over 90% of the suspended bacteria flocculate within seconds of being mixed with chitosan nanoparticles of a highly positive surface charge. Finally, the nanoparticles are significantly more efficient as a clustering agent compared to an equal mass of molecular chitosan in solution, as the bacteria-nanoparticle clusters formed are substantially larger. The bacteria-nanoparticle aggregation effect demonstrated here promises a rapid separation method for aiding pathogen detection and for flocculation of bacteria in fermentation processes. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009.

PMID: 19565661 [found with GoPubMed]

6: Colloids Surf B Biointerfaces 2009 Jun:

Effect of surface charge and agglomerate degree of magnetic iron oxide nanoparticles on KB cellular uptake in vitro.

Ge, Y; Zhang, Y; Xia, J; Ma, M; He, S; Nie, F; Gu, N

State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.

We synthesized three types of magnetic iron oxide nanoparticles (MNPs), which were meso-2,3-dimercaptosuccinic acid (DMSA) coated MNPs (DMSA@MNPs, 17.3+/-4.8nm, negative charge), chitosan (CS) coated MNPs (CS@MNPs, 16.5+/-6.1nm, positive charge) and magnetic nanoparticles agglomerates, formed by electronic aggregation between DMSA@MNPs and CS (CS-DMSA@MNPs, 85.7+/-72.9nm, positive charge) respectively. The interactions of these MNPs with Oral Squamous Carcinoma Cell KB were investigated. The results showed that cellular uptakes of MNPs were on the dependence of incubation time, nanoparticles concentration and nanoparticles properties such as surface charge, size, etc. The cellular uptake was enhanced with the increase of incubation time and nanoparticles concentration. Although all MNPs could enter to cells, we observed apparent differences in the magnitude of nanoparticles uptaken. The cellular uptake of CS-DMSA@MNPs by KB cells was the highest and that of DMSA@MNPs was the lowest among the three types of MNPs. The same conclusions were drawn via the reduction of water proton relaxation times T(2)(*), resulting from the different iron load of labeled cells using a 1.5T clinical MR imager. The finding of this study will have implications in the chemical design of nanomaterials for biomedical applications.

PMID: 19564099 [found with GoPubMed]

7: J Control Release 2009 Jun:

Hydrotropic oligomer-conjugated glycol chitosan as a carrier of paxclitaxel: Synthesis, characterization, and in vivo biodistribution.

Saravanakumar, G; Min, K H; Min, D S; Kim, A Y; Lee, C M; Cho, Y W; Lee, S C; Kim, K; Jeong, S Y; Park, K; Park, J H; Kwon, I C

Department of Advanced Polymer and Fiber Materials, Kyung Hee University, Gyeonggi-do 446-701, Korea.

Development of successful formulations for poorly water-soluble drugs remains a longstanding critical and challenging issue in cancer therapy. As a potential drug carrier of paclitaxel, hydrotropic oligomer-glycol chitosan (HO-GC) was synthesized by chemical conjugation of the N,N-diethylnicotinamide-based oligomer, uniquely designed for enhancing the aqueous solubility of paclitaxel, to the backbone of glycol chitosan. Owing to its amphiphilicity, the conjugate formed self-assembled nanoparticles with a mean diameter of 313+/-13 nm in a phosphate-buffered saline (PBS, pH 7.4 at 37 degrees C). HO-GC nanoparticles maintained their structure for up to 50 days in a PBS. They could encapsulate a high quantity (20 wt%) of paclitaxel (PTX) with a maximum drug loading efficiency of 97%, due to the presence of hydrotropic inner cores. When HO-GC-PTX particles were exposed to the 0.1M sodium salicylate solution in PBS (pH 7.4), PTX was released from nanoparticles in a sustained manner. From the cytotoxicity test, it was confirmed that HO-GC-PTX nanoparticles showed lower cytotoxicity than free PTX formulation in 50%/50% Cremophor EL/ethanol mixture. The optical imaging results indicated that near-infrared fluorescence dye (Cy5.5)-labeled HO-GC-PTX showed an excellent tumor specificity in SCC7 tumor-bearing mice, due to the enhanced permeation and retention effect. Overall, HO-GC-PTX nanoparticles might be a promising carrier for PTX delivery in cancer therapy.

PMID: 19560497 [found with GoPubMed]

8: Biomacromolecules 2009 Jun:

Chitosan-Alginate Blended Nanoparticles as Carriers for the Transmucosal Delivery of Macromolecules.

Goycoolea, F M; Lollo, G; Remuñán-López, C; Quaglia, F; Alonso, M J

Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Spain, CIAD, Laboratory of Biopolymers, P.O. Box 1735, Hermosillo, 83000 Mexico, and Department of Pharmaceutical and Toxicological Chemistry, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.

Nanoparticles intended for use in the transmucosal delivery of macromolecules were prepared by the ionic gelation of chitosan (CS) hydrochloride with pentasodium tripolyphosphate (TPP) and concomitant complexation with sodium alginate (ALG). The incorporation of a small proportion of ALG of increasing molecular weight (M(w); from 4 to 74 kDa) into the nanoparticles led to a monotonic increase in colloidal size from approximately 260 to approximately 525 nm. This increase in size was regarded as a consequence of the formation of gradually more expanded structures. Insulin, taken as a model peptide, was associated to CS-TPP-ALG nanoparticles with efficiencies in the range of approximately 41 to approximately 52%, irrespective of the M(w) of the ALG incorporated in the formulation. These CS-TPP-ALG nanoparticles exhibited a capacity to enhance the systemic absorption of insulin after nasal administration to conscious rabbits. Interestingly, it was observed that the duration of the hypoglycaemic response was affected by the ALG's M(w). Briefly, this work describes a new nanoparticulate composition of potential value for increasing nasal insulin absorption.

PMID: 19545119 [found with GoPubMed]

9: Acta Biomater 2009 Jun:

Hollow and Degradable Polyelectrolyte Nanocapsules for Protein Drug Delivery.

Shu, S; Sun, C; Zhang, X; Wu, Z; Wang, Z; Li, C

Key Laboratory of Functional Polymer Materials Ministry of Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, P.R.China and Metabolic Diseases Hospital, Tianjin Medical University, Tianjin 300070, P.R. China.

Biodegradable hollow capsules encapsulating protein drugs were prepared via layer-by-layer assembly of water soluble chitosan (WSC) and dextran sulfate (DS) on protein entrapping amino functionalized silica particles and the subsequent removal of the silica. In order to enhance the encapsulated efficiency and decrease its burst release, we designed this new system to fulfill these two goals. Bovine serum albumin (BSA), which was used as model protein, was entrapped into the nanocapsules. This system demonstrated good capacity for the encapsulation and loading of BSA. The burst release was decreased to lower than 10 % in phosphate buffered saline within 2 h. No significant conformation change was noted from the released BSA in comparison with native BSA by using circular dichroism spectroscopy. Cell viability study suggested that the nanocapsules had good biocompatibility. The drug release kinetics mechanism is Fickian diffusion. This kind of novel composite nanocapsules may be a promising delivery system for water soluble proteins and peptides.

PMID: 19531385 [found with GoPubMed]

10: Drug Dev Ind Pharm 2009 Jun35(6):719-26

Ultrafine chitosan nanoparticles as an efficient nucleic acid delivery system targeting neuronal cells.

Malhotra, Meenakshi; Kulamarva, Arun; Sebak, Safaa; Paul, Arghya; Bhathena, Jasmine; Mirzaei, Maryam; Prakash, Satya

Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering and Physiology, Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.

Background: Cell transfection with nanoscaled cationic polymeric particles using Chitosan has been extensively explored. Because of its properties such as cationic charges, biocompatibility, biodegradability, and low toxicity, it has been used as a potential gene, siRNA, protein (including antibodies), and drug carrier system. Method: This work describes the development of chitosan nanoparticles of a 20-nm diameter for a potential siRNA delivery application. The particles were prepared using an ionic gelation method, using sodium tripolyphosphate as a cross-linker. The effect of variation in pH was investigated on particle size and surface charge. Gene loading efficiency by chitosan nanoparticles was performed by varying weight ratios of chitosan : siRNA. Transfection efficiency was evaluated on Neuro2a cells. Results: It was observed that 20-nm-sized nanoscale complexes induced significant transfection in neuronal cells. Conclusion: These particles have potential in the delivery of siRNA to neural tissues.

PMID: 19514987 [found with GoPubMed]

11: Eur J Pharm Biopharm 2009 Jun:

Design for optimization of nanoparticles integrating biomaterials for orally dosed insulin.

Woitiski, C B; Veiga, F; Ribeiro, A; Neufeld, R

Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.

Design of nanoparticles integrating biomaterials that govern the functional behavior of orally dosed insulin is focused on improving insulin stability and absorption by facilitating its uptake and translocation throughout the gastrointestinal tract, while providing protection from acidic and enzymatic degradation. The purpose of the study was to optimize a nanoparticle formulation by investigating the relationship between design factors and experimental data by response surface methodology. Designed nanoparticles consisting of calcium crosslinked alginate, dextran sulfate, poloxamer 188 and chitosan followed by an outermost coating of albumin are described as multilayer complex retaining insulin within the nanoparticle. A 3-factor 3-level Box-Behnken design was used to optimize nanoparticle formulation. The screened independent variables were the concentration of calcium chloride, chitosan and albumin, and the dependent variables were particle size, polydispersity index, zeta potential, entrapment efficiency and insulin release in enzyme-free simulated digestive fluids. Experimental responses of a total of 15 formulations resulted in mean nanoparticle diameters ranging from 394 to 588 nm, with polydispersity index from 0.77 to 1.10, zeta potential values ranging from -36.6 to -44.5 mV, and entrapment efficiency of insulin over 85%. Insulin release from nanoparticles in enzyme-free digestive fluids was prevented during 120 minutes in gastric conditions, and over 80% of insulin was released after 180 minutes in simulated intestinal fluid. Based on the experimental responses and the criteria of desirability defined by constraints, solutions of 0.20% calcium chloride, 0.04% chitosan and 0.47% albumin constitute the optimum formulation of nanoparticles for orally dosed insulin.

PMID: 19508892 [found with GoPubMed]

12: J Pharm Pharmacol 2009 Jun61(6):713-9

Polymeric nanoparticles of cholesterol-modified glycol chitosan for doxorubicin delivery: preparation and in-vitro and in-vivo characterization.

Yu, Jing-Mou; Li, Yong-Jie; Qiu, Li-Yan; Jin, Yi

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

OBJECTIVES: Polymeric nanoparticles have been extensively studied as drug carriers. Chitosan and its derivatives have attracted significant attention in this regard but have limited application because of insolubility in biological solution. In this work, we attempted to utilize cholesterol-modified glycol chitosan (CHGC) self-aggregated nanoparticles to increase aqueous solubility, and to reduce side effects and enhance the antitumour efficacy of the anticancer drug doxorubicin. Methods CHGC nanoparticles were loaded with doxorubicin by a dialysis method, and their characteristics were determined by transmission electron microscopy examination, light-scattering study, in-vitro drug-release study, pharmacokinetic study in rats and in-vivo antitumour activity in mice. KEY FINDINGS: The resulting doxorubicin-loaded CHGC nanoparticles (DCNs) formed self-assembled aggregates in aqueous medium. From the observation by transmission electron microscopy, DCNs were almost spherical in shape. The mean diameters of these nanoparticles determined by dynamic light scattering were in the range of 237-336 nm as the doxorubicin-loading content increased from 1.73% to 9.36%. In-vitro data indicated that doxorubicin release from DCNs was much faster in phosphate-buffered saline at pH 5.5 than at pH 6.5 and 7.4, and the release rate was dependent on the loading content of doxorubicin in these nanoparticles. It was observed that DCN-16 (drug loaded content: 9.36%) exhibited prolonged circulation time in rat plasma and showed higher antitumour efficacy against S180-bearing mice than free doxorubicin. CONCLUSIONS: These results indicated that CHGC nanoparticles had potential as a carrier for insoluble anticancer drugs in cancer therapy.

PMID: 19505361 [found with GoPubMed]

13: Acta Biochim Biophys Sin (Shanghai) 2009 Jun41(6):515-26

Chitosan nanoparticles as non-viral gene delivery vehicles based on atomic force microscopy study.

Yuan, Yujing; Tan, Jieyi; Wang, Yifei; Qian, Chuiwen; Zhang, Meiying

Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510630, China.

Chitosan (CS), a biocompatible and biodegradable material, can act as a non-viral delivery vehicle with low toxicity. In this study, plasmid DNA (pDNA) and siRNA were encapsulated in CS nanoparticles (NPs) to prepare CS-DNA and CS-siRNA NPs using a complex coacervation process. The CS-DNA particle size was within the range of 180-370 nm with a surface charge ranging from 0 to 18 mV at pH 5.5. The stability of pDNA in CS-DNA was investigated by pDNA release study and DNase I protection assay. The release of pDNA from NPs was studied in pH 7.4 phosphatebuffered saline at 378C and the CS-DNA NPs could delay the DNA release. Results of DNase I protection assay showed that CS-DNA NPs could protect the encapsulated pDNA from nuclease degradation. In the transfection study, it was found that the transfection efficiency in vitro was dependent on the molecular weight, charge ratio, and DNA concentration of the CS-DNA NP as well as the type of cell transfected. Moreover, the morphology of HeLa cells transfected with CS-siRNA complexes was studied using atomic force microscopy. The results suggest that CS may be more capable than liposome in delivering siRNA to target cells. In summary, our analysis suggests that pDNA and siRNA can be encapsulated in CS NPs without being damaged.

PMID: 19499155 [found with GoPubMed]

14: Int J Pharm 2009 Jun375(1-2):97-106

The potential of glycol chitosan nanoparticles as carrier for low water soluble drugs.

Trapani, Adriana; Sitterberg, Johannes; Bakowsky, Udo; Kissel, Thomas

Facoltà di Farmacia, Dipartimento Farmaco-Chimico, Università degli Studi di Bari, via Orabona 4, 70125 Bari, Italy.

The laser dye 6-coumarin was selected as model of low water soluble drug to be encapsulated in glycol chitosan nanoparticles intended for transmucosal applications and, at the same time, being a fluorescent probe, it is of aid to elucidate the intracellular fate of the particles. To increase the aqueous solubility of the tracer, the complexation with different cyclodextrins was adopted. The fluorescence properties of the inclusion complexes were evaluated. The increase in aqueous solubility provided by different cyclodextrins [up to 1.4x10(-4) M in the case of heptakis (2,6-di-O-methyl)-beta-cyclodextrin] allowed the preparation of novel glycol chitosan nanoparticles according to the ionic cross-linking of the polycation by sodium tripolyphosphate. Small changes in the preparation technique allowed to produce particles of two different sizes, around 200 nm and bigger than 300 nm where the contribution of cyclodextrin consisted of the modulation encapsulation efficiency in the final particles. Confocal laser scanning microphotographs clearly showed the internalization of 6-coumarin nanoparticles in Caco-2 cell line. The results reveal that these biodegradable nanoparticles hold promise as probes in biomedical field.

PMID: 19481695 [found with GoPubMed]

15: Anal Chim Acta 2009 Jun644(1-2):72-7

The preparation of reagentless electrochemical immunosensor based on a nano-gold and chitosan hybrid film for human chorionic gonadotrophin.

Yang, Guangming; Chang, Yanbing; Yang, Hua; Tan, Lin; Wu, Zaisheng; Lu, Xuxiao; Yang, Yunhui

College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming 650092, PR China.

A novel amperometric immunosensor for determination of human serum chorionic gonadotrophin (hCG) was constructed by immobilizing hCG antibody with nano-gold and chitosan (CHIT) hybrid film electrochemical co-deposited on a glassy carbon electrode. The fabricated procedures and electrochemical behaviors of proteins on such an interface were characterized with electrochemical impedance, cyclic voltammetry and chronoamperometry. The effect of incubation time on the electrochemical behavior of immunosensor was studied and other experimental conditions such as mass ratio of CHIT and HAuCl4, depositing time of hybrid film, the pH, and temperature were studied too. The current response of the immunosensor is in linear relationship with concentration of hCG. The resulting immunosensor offers an excellent amperometric response for hCG ranging from 0.20 to 100 mIU mL(-1) with a detection limit of 0.1 mIU mL(-1). A satisfactory determination of hCG in serum samples can be obtained by this immunosensor.

PMID: 19463565 [found with GoPubMed]

16: Int J Pharm 2009 Jun374(1-2):119-24

Preventing the thermal degradation of astaxanthin through nanoencapsulation.

Tachaprutinun, Amornset; Udomsup, Thanchanok; Luadthong, Chuleeporn; Wanichwecharungruang, Supason

Sensor Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.

The encapsulation of astaxanthin into polymeric nanospheres by solvent displacement was compared for three chemically diverse polymers, namely; poly(ethylene oxide)-4-methoxycinnamoylphthaloylchitosan (PCPLC), poly(vinylalcohol-co-vinyl-4-methoxycinnamate) (PB4) and ethylcellulose (EC). Although capable of forming nanospheres themselves, EC could not encapsulate astaxanthin at all, whilst PB4 yielded a poor encapsulation efficiency. In contrast, PCPLC yielded reasonably good encapsulation efficiency (98%) at a loading of 40% (w/w). Moreover, the freeze-dried astaxanthin-encapsulated PCPLC nanospheres showed good dispersibility in water yielding stable aqueous suspensions of 300-320 nm nanoparticles. A steady release of astaxanthin from the nanospheres up to a maximum of approximately 85% payload over 60 min was also demonstrated, at least in acetone. NMR analysis indicated that after a two-hour-heating at 70 degrees C in an aqueous environment, PCPLC nanoencapsulated astaxanthin showed minimal heat degradation of olefinic functionality in contrast to that of the unencapsulated pigment molecules which were almost completely destroyed.

PMID: 19446768 [found with GoPubMed]

17: Oligonucleotides 2009 Jun19(2):163-8

Naked siLNA-mediated gene silencing of lung bronchoepithelium EGFP expression after intravenous administration.

Glud, Sys Zoffmann; Bramsen, Jesper B; Dagnaes-Hansen, Frederik; Wengel, Jesper; Howard, Kenneth Alan; Nyengaard, Jens R; Kjems, Jørgen

Interdisciplinary Nanoscience Center, Arhus University, Arhus, Denmark.

The use of systemic siRNA therapeutics for RNA interference-mediated silencing of disease genes is limited by serum instability and inadequate biodistribution. We have previously reported on the EGFP gene silencing effect of chitosan/siRNA nanoparticles in the bronchoepithelium of mice lungs following intranasal delivery and improved serum stability and reduced off-targeting effects in vitro by incorporation of locked nucleic acid (LNA). In this study, we examine the pulmonary gene silencing effect of siLNAs targeting enhanced-green-fluorescent-protein (EGFP) in lung bronchoepithelium upon intravenous delivery of naked siLNAs and upon intranasal delivery of either naked siLNA or chitosan/siLNA nanoparticles. We show that naked siLNA administered intravenously efficiently reduces the EGFP protein expression. A similar effect is obtained with intranasal delivery of chitosan nanoparticles containing siLNA whereas intranasally instilled naked siLNA did not cause a knockdown.

PMID: 19441893 [found with GoPubMed]

18: Int J Food Microbiol 2009 Jun132(2-3):127-33

Oleoyl-chitosan nanoparticles inhibits Escherichia coli and Staphylococcus aureus by damaging the cell membrane and putative binding to extracellular or intracellular targets.

Xing, Ke; Chen, Xi Guang; Liu, Cheng Sheng; Cha, Dong Su; Park, Hyun Jin

College of Marine Life Science, Ocean University of China, 5# Yushan Road, Qingdao 266003, PR China.

A novel chitosan antibacterial dispersion system was prepared by oleoyl-chitosan (OCS) nanoparticles (OCNP). We further investigated the antimicrobial mode of OCNP against Escherichia coli and Staphylococcus aureus using a combination of approaches, including measurement of the effect of lecithin and phosphate groups, the conformation of membrane protein, internalization of fluorescein isothiocyanate (FITC)-labeled OCS nanoparticles (FITC-OCS nanoparticles) observed under fluorescence microscopy and DNA/RNA binding assay. Results of fluorescence experiments indicated that OCNP influenced the structure of bacterial membranes. The lecithin effect showed that OCNP bound to cytoplasmic membrane phospholipids of S. aureus, and phosphate groups played an important role. Fluorescence microscopy observations demonstrated that the way OCNP entered into bacteria varied against strains. The gel-retardation experiment showed that OCNP bound strongly to DNA/RNA and retarded their migration in the gels in a concentration-dependent manner. These results indicate that OCNP exerts its antibacterial activity by damaging the structures of cell membrane and putative binding to extracellular targets such as phosphate groups or intracellular targets such as DNA and RNA.

PMID: 19439383 [found with GoPubMed]

19: Nanotechnology 2009 Jun20(22):225108

Hybrid polymeric hydrogels for ocular drug delivery: nanoparticulate systems from copolymers of acrylic acid-functionalized chitosan and N-isopropylacrylamide or 2-hydroxyethyl methacrylate.

Barbu, Eugen; Verestiuc, Liliana; Iancu, Mihaela; Jatariu, Anca; Lungu, Adriana; Tsibouklis, John

School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael's Building, White Swan Road, Portsmouth PO12DT, UK.

Nanoparticulate hybrid polymeric hydrogels (10-70 nm) have been obtained via the radical-induced co-polymerization of acrylic acid-functionalized chitosan with either N-isopropylacrylamide or 2-hydroxyethyl methacrylate, and the materials have been investigated for their ability to act as controlled release vehicles in ophthalmic drug delivery. Studies on the effects of network structure upon swelling properties, adhesiveness to substrates that mimic mucosal surfaces and biodegradability, coupled with in vitro drug release investigations employing ophthalmic drugs with differing aqueous solubilities, have identified nanoparticle compositions for each of the candidate drug molecules. The hybrid nanoparticles combine the temperature sensitivity of N-isopropylacrylamide or the good swelling characteristics of 2-hydroxyethyl methacrylate with the susceptibility of chitosan to lysozyme-induced biodegradation.

PMID: 19433871 [found with GoPubMed]

20: Int J Biol Macromol 2009 Jun44(5):408-12

Chitosan-SiO2-multiwall carbon nanotubes nanocomposite: a novel matrix for the immobilization of creatine amidinohydrolase.

Tiwari, Ashutosh; Dhakate, Sanjay R

Division of Engineering Materials, National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012, India.

A matrix made up of chitosan-SiO(2)-multiwall carbon nanotubes (CHIT-SiO(2)-MWCNTs) nanocomposite was fabricated to investigate the immobilization of creatine amidinohydrolase (CAH). CAH enzyme was covalently immobilized with the CHIT-SiO(2)-MWCNTs matrix using glutaraldehyde as a linker. The resulting CAH/CHIT-SiO(2)-MWCNTs biomatrix was characterized with Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and cyclic voltammetry (CV) taking CHIT-SiO(2)-MWNTs as a reference. The influence of various parameters on CAH enzyme activity within the matrix was investigated including pH, temperature, and time. The Michaelis-Menten constant and apparent activities for the CAH enzyme were calculated to be 0.58 mM and 83.16 mg/cm(2), respectively; indicating CHIT-SiO(2)-MWCNTs nanocomposite matrix has a high affinity to immobilize CAH enzyme.

PMID: 19428474 [found with GoPubMed]

21: Biomacromolecules 2009 Jun10(6):1642-9

Asymmetric chitosan membrane containing collagen I nanospheres for skin tissue engineering.

Chen, Kuo-Yu; Liao, Wei-Ju; Kuo, Shyh-Ming; Tsai, Fuu-Jen; Chen, Yueh-Sheng; Huang, Chih-Yang; Yao, Chun-Hsu

Department of Chemical and Materials Engineering, National Yunlin University of Science and Technology, Yunlin, Taiwan.

A biodegradable chitosan membrane with an asymmetric structure, seeded with fibroblasts, was prepared as a novel skin substitute. Chitosan was cross-linked with genipin and then frozen and lyophilized to yield a porous asymmetric membrane (CG membrane). Nanoscale collagen I particles were injected into the CG membrane to form an asymmetric CGC membrane. The results reveal that the CG membrane treated with 0.125 wt % of genipin had a higher swelling ratio, porosity, and pore size. After 7 d of dynamic culture, many of the adhered cells exhibited a flat morphology and well spread on the surface of CGC membrane treated with 0.125 wt % of genipin. In animal studies, the CGC membrane seeded with fibroblasts and grown in vitro for 7 d was more effective than both gauze and commercial wound dressing, Suile, in healing wounds. An in vivo histological assessment indicated that covering the wound with the asymmetric CGC membrane resulted in its epithelialization and reconstruction. CGC membrane, thus, has great potential in skin tissue engineering.

PMID: 19419166 [found with GoPubMed]

22: Chemistry 2009 Jun15(24):5935-41

Controlled assembly of Au, Ag, and Pt nanoparticles with chitosan.

Hong, Min; Wu, Linlin; Tian, Liangfei; Zhu, Jin

Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, State Key Laboratory of Coordination Chemistry, Nanjing National Laboratory of Microstructures, Nanjing University, Nanjing 210093, PR China.

A simple method for the controlled assembly of metal nanoparticles into one-dimensional chains has been developed. The chain-formation process could be accounted for by the electrostatic interaction of the negatively charged carboxylic groups on the citrate ions surrounding metal nanoparticles and the positively charged chitosan polymer. Three representative types of nanoparticles comprising Au, Ag, and Pt, respectively, have been used to illustrate the generic applicability of the proposed methodology. Facile control of the chain length of the nanoparticle assembly could be achieved by adjusting the concentrations of negatively or positively charged species. We anticipate the ready adaptability of the methodology to nanoparticles of more complex compositions.

PMID: 19418520 [found with GoPubMed]

23: Biomacromolecules 2009 Jun10(6):1429-35

Non-cytotoxic silver nanoparticle-polysaccharide nanocomposites with antimicrobial activity.

Travan, Andrea; Pelillo, Chiara; Donati, Ivan; Marsich, Eleonora; Benincasa, Monica; Scarpa, Tommaso; Semeraro, Sabrina; Turco, Gianluca; Gennaro, Renato; Paoletti, Sergio

Department of Life Sciences, University of Trieste, Trieste, Italy.

In this work we study (i) the formation and stabilization of silver nanoparticles in a bioactive chitosan-derived polysaccharide solution, (ii) the antimicrobial properties, either in solution or in 3D hydrogel structures, obtained by mixtures with the polysaccharide alginate, and (iii) the cytotoxicity of the latter nanocomposite materials on different eukaryotic cell lines. Antimicrobial results show that these nanocomposite systems display a very effective bactericidal activity toward both Gram+ and Gram- bacteria. However, the hydrogel does not show any cytotoxic effect toward three different eukaryotic cell lines. This is due to the fact that the nanoparticles, immobilized in the gel matrix, can exert their antimicrobial activity by simple contact with the bacterial membrane, while they can not be uptaken and internalized by eukaryotic cells. This novel finding could advantageously contribute to responding to the growing concerns on the toxicity of nanoparticles and facilitate the use of silver-biopolymer composites in the preparation of biomaterials.

PMID: 19405545 [found with GoPubMed]

24: Biomacromolecules 2009 Jun10(6):1627-32

Cross-linked chitosan/chitin crystal nanocomposites with improved permeation selectivity and pH stability.

Mathew, Aji P; Laborie, Marie-Pierre G; Oksman, Kristiina

Division of Manufacturing and Design of Wood and Bionanocomposites, Luleå University of Technology, Skellefteå, Sweden.

This study is aimed at developing and characterizing cross-linked bionanocomposites for membrane applications using chitosan as the matrix, chitin nanocrystals as the functional phase, and gluteraldehyde as the cross-linker. The nanocomposites' chemistry and morphology were examined by estimation of gel content, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and atomic force microscopy (AFM), whereby the occurrence of cross-linking and nanoscale dispersion of chitin in the matrix was confirmed. Besides, cross-linking and chitin whiskers content were both found to impact the water uptake mechanism. Cross-linking provided dimensional stability in acidic medium and significantly decreased the equilibrium water uptake. Incorporation of chitin nanocrystals provided increased permeation selectivity to chitosan in neutral and acidic medium.

PMID: 19388678 [found with GoPubMed]

25: Biomacromolecules 2009 Jun10(6):1402-9

Polysaccharide-based polyelectrolyte complex nanoparticles from chitosan, heparin, and hyaluronan.

Boddohi, Soheil; Moore, Nicholas; Johnson, Patrick A; Kipper, Matt J

Department of Chemical and Biological Engineering and School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523, USA.

The formation of polyelectrolyte complex nanoparticles (PCN) was investigated at different charge mixing ratios for the chitosan-heparin (chi-hep) and chitosan-hyaluronan (chi-ha) polycation-polyanion pairs. The range of 0.08-19.2 for charge mixing ratio (n(+)/n(-)) was examined. The one-shot addition of polycation and polyanion solutions used for the formation of the PCN permitted formation of both cationic and anionic particles from both polysaccharide pairs. The influence of the charge mixing ratio on the size and zeta potential of the particles was investigated. The morphology and stability of the particles when adsorbed to surfaces was studied by scanning electron microscopy (SEM). For most conditions studied, colloidally stable, nonstoichiometric PCN were formed in solution. However, PCN formation was inhibited by flocculation at charge mixing ratios near 1. When adsorbed to surfaces and dried, some formulations resulted in discrete nanoparticles, while others partially or completely aggregated or coalesced, leading to different surface morphologies.

PMID: 19371056 [found with GoPubMed]

26: Biosens Bioelectron 2009 Jun24(10):2991-6

A nitrite biosensor based on the immobilization of cytochrome c on multi-walled carbon nanotubes-PAMAM-chitosan nanocomposite modified glass carbon electrode.

Chen, Quanpeng; Ai, Shiyun; Zhu, Xiangbin; Yin, Huanshun; Ma, Qiang; Qiu, Yanyan

College of Resources and Environment, Shandong Agricultural University, Taian 271018, Shandong, PR China.

A novel nitrite biosensor was successfully prepared via immobilizing Cytochrome c (Cyt c) onto the multi-walled carbon nanotubes-poly(amidoamine) (PAMAM)-chitosan (MWNT-PAMAM-Chit) nanocomposite modified glass carbon electrode (GCE). Ultraviolet and visible (UV-vis) absorption spectrum, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to examine the native conformation and bioactivity of the immobilized Cyt c, and the electrochemical properties of the modified electrodes, respectively. The results indicate that the immobilized Cyt c retained its native characters, and the MWNT-PAMAM-Chit nanocomposite is a good platform for the immobilization of Cyt c as well as an excellent promoter for the electron transfer between Cyt c and electrode. The high reactive Cyt c pi-cation, which can oxidize NO(2)(-) into NO(3)(-) in the solution, is generated at higher potential (>0.7 V) based on the further oxidation of Cyt c. The nitrite biosensor showed a fast response to nitrite (about 5 s) in two concentration intervals, one was from 0.1 to 29 microM, and the other from 29 to 254 microM. The low detection limit of 0.01 microM was obtained.

PMID: 19345570 [found with GoPubMed]

27: Anal Bioanal Chem 2009 Jun394(3):855-61

Disposable DNA biosensor with the carbon nanotubes-polyethyleneimine interface at a screen-printed carbon electrode for tests of DNA layer damage by quinazolines.

Galandová, Júlia; Ovádeková, Renáta; Ferancová, Adriana; Labuda, Ján

Institute of Analytical Chemistry, Slovak University of Technology in Bratislava, Radlinského 9, 812 37, Bratislava, Slovakia.

A screen-printed carbon working electrode within a commercially available screen-printed three-electrode assembly was modified by using a composite of multiwalled carbon nanotubes (MWCNT) dispersed in polyethylenimine (PEI) followed by covering with the calf thymus dsDNA layer. Several electrochemical methods were used to characterize the biosensor and to evaluate damage to the surface-attached DNA: square wave voltammetry of the [Ru(bpy)(3)](2+) redox indicator and mediator of the guanine moiety oxidation, cyclic voltammetry and electrochemical impedance spectroscopy in the presence of the [Fe(CN)(6)](3-/4-) indicator in solution. Due to high electroconductivity and large surface area of MWCNT and positive charge of PEI, the MWCNT-PEI composite is an advantageous platform for the DNA immobilization by the polyelectrolyte complexation and its voltammetric and impedimetric detection. In this respect, the MWCNT-PEI interface exhibited better properties than the MWCNT-chitosan one reported from our laboratory previously. A deep DNA layer damage at incubation of the biosensor in quinazoline solution was found, which depends on the quinazoline concentration and incubation time.

PMID: 19306115 [found with GoPubMed]

28: Acta Biomater 2009 Jun5(5):1489-98

Polysaccharide surface modified Fe3O4 nanoparticles for camptothecin loading and release.

Zhu, Aiping; Yuan, Lanhua; Jin, Wenjie; Dai, Sheng; Wang, Qianqian; Xue, Zhengfeng; Qin, Aijian

College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, PR China.

Fe(3)O(4) nanoparticles were stabilized using different functional polysaccharides, such as chitosan (CS), O-carboxymethylchitosan (OCMCS) and (N-succinyl-O-carboxymethylchitosan (NSOCMCS) to improve their bioactivity. The release profile and the in vitro cancer cell inhibition activity of camptothecin (CPT) loaded polysaccharide modified Fe(3)O(4) nanoparticles were systematically studies. The particle size and size distribution of CPT-loaded polysaccharide modified Fe(3)O(4) nanoparticles were found to be strongly dependent on polysaccharide character. Such polysaccharide character could also affect CPT adsorption efficiency, CPT release behavior and bovine serum albumin (BSA) unspecific binding capacity. After 24 h incubation of 7721 cancer cells with CPT-loaded polysaccharide modified Fe(3)O(4) nanoparticles, significant changes in cell morphology could be discernible from phase contrast microscopy. Cytotoxicity assay showed these polysaccharide modified Fe(3)O(4) nanoparticles did not exhibit noteworthy cytotoxicity against 7721, however, the in vitro inhibition rate of CPT-loaded polysaccharide modified Fe(3)O(4) nanoparticles against 7721 liver cancer cell increased significantly in comparison with that of CPT-free drug.

PMID: 19286431 [found with GoPubMed]

29: J Tissue Eng Regen Med 2009 Jun3(4):243-54

Electrostatic binding of nanoparticles to mesenchymal stem cells via high molecular weight polyelectrolyte chains.

Heng, Boon C; Cowan, Catherine M; Davalian, Dariush; Stankus, John; Duong-Hong, Duc; Ehrenreich, Kevin; Basu, Shubhayu

Abbott Vascular Inc., Santa Clara, CA 95054, USA.

Combining stem cell transplantation with nanoparticle-mediated delivery of drugs and pharmaceuticals is envisioned to be one of the next major developmental steps in regenerative medicine. However, a major challenge would be to keep nanoparticles co-localized with stem cells upon transplantation or transfusion in situ. Since nanoparticles are physically much smaller in size than cells and would not specifically bind to extracellular matrix, it is easier for them to disperse from the transplantation site via the blood circulation. Conjugating nanoparticles directly to the cell membrane can potentially interfere with cellular function by physically obstructing cell surface receptors from interacting with the extracellular matrix, various growth factors and cytokines and other cells. Moreover, drug-loaded nanoparticles may be internalized into the cytoplasm via endocytosis or phagocytosis, which may wreak damage on the cellular machinery, leading to impaired physiological function or cell death. A novel solution may be to utilize high molecular weight polyelectrolyte chains to electrostatically bind nanoparticles to cells. For this purpose, hyaluronan, poly-L-lysine and chitosan are of special interest, because these molecules are generally recognized to be biocompatible for application in various pharmaceutical and surgical products. This study investigated the use of these molecules to bind nanoparticles to mesenchymal stem cells (MSCs), and a novel technique of conjugating half the cell surface with nanoparticles through the use of polyelectrolyte chains was also developed. This would avoid blocking MSC interaction with cytokines, growth factors, extracellular matrix and other cells within the recipient tissue/organ upon delivery in situ.

PMID: 19283725 [found with GoPubMed]

30: Nanomedicine 2009 Jun5(2):208-15

Preparation and in vitro evaluation of mucoadhesion and permeation enhancement of thiolated chitosan-pHEMA core-shell nanoparticles.

Moghaddam, Firooze Aghaei; Atyabi, Fatemeh; Dinarvand, Rassoul

Novel Drug Delivery Systems Laboratory, Faculty of Pharmacy, Medical Sciences/University of Tehran, Tehran, Iran.

The aim of the present work was to evaluate the in vitro mucoadhesion and permeation enhancement properties of thiolated chitosan (chitosan-glutathione) coated poly(hydroxyl ethyl methacrylate) nanoparticles. Core-shell nanoparticles were prepared by radical emulsion polymerization method initiated by cerium(IV) ammonium nitrate. Different molecular weights of chitosan were utilized for nanoparticles preparation. The physicochemical properties of nanoparticles were characterized by size, zeta potential, and thiol content. Incorporation of fluorescein isothiocyanate dextran (FD4, MW 4400 Da), which was used as the model macromolecule, was achieved by incubation method. The intestinal mucoadhesion and penetration enhancement properties of nanoparticles were investigated using excised rat jejunum. All nanoparticle systems showed mucoadhesion and improved apparent permeation coefficient (P(app)) of FD4. Nanoparticles prepared by thiolated chitosan with medium molecular weight revealed the most mucoadhesion and penetration enhancement properties.

PMID: 19186220 [found with GoPubMed]

31: J Mater Sci Mater Med 2009 Jun20(6):1315-20

pH-sensitive nanoparticles self-assembled from a novel class of biodegradable amphiphilic copolymers based on chitosan.

Cai, Guoqiang; Jiang, Hongliang

Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People's Republic of China.

A new type of biodegradable amphiphilic graft copolymers, PEG-g-hexanoyl chitosan, was synthesized by a facile scheme. The self-assemble properties of the copolymers were studied by TEM, fluorometry and dynamic light scattering. It was found that spherical nanoparticles of the copolymers could be formed through dialysis method. With the increase of PEG content in the copolymers, the average diameter of the nanoparticles decreased from about 180 to 40 nm. PEG fraction in the copolymers has little effect on the copolymer CAC. The micellization of the copolymers was strongly dependent of the medium pH. When pH was lowered from 7.2 to 6.8, the average diameter of the nanoparticles dramatically changed from about 180 to 60 nm.

PMID: 19132500 [found with GoPubMed]

32: J Hazard Mater 2009 Jun165(1-3):664-9

Catalytic reduction of 4-nitrophenol by magnetically recoverable Au nanocatalyst.

Chang, Yang-Chuang; Chen, Dong-Hwang

Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan.

A novel magnetically recoverable Au nanocatalyst was fabricated by the simple adsorption-reduction of Au(III) ions on chitosan-coated iron oxide magnetic nanocarrier. Au nanoparticles with a mean diameter of 3.14 nm were well loaded on the surface of magnetic nanocarrier because chitosan layer provided an effective driving force in the formation and stabilization of Au nanoparticles. The resultant magnetically recoverable Au nanocatalyst exhibited excellent catalytic activity to the reduction of 4-nitrophenol (4-NP) with sodium borohydride. The rate constants evaluated in terms of pseudo-first-order kinetic model increased with increasing the amount of Au nanocatalyst, decreasing the initial 4-NP concentration, and increasing the temperature. Also, the kinetic data suggested that this catalytic reaction was diffusion controlled owing to the presence of chitosan layer. In addition, catalyst reuse showed no trace of deactivation or poisoning during the catalytic and separation processes, revealing the stable nature and good catalytic ability of this nanocatalyst.

PMID: 19022566 [found with GoPubMed]

33: Eur J Pharm Biopharm 2009 Jun72(2):358-69

The influence of chitosan content in cationic chitosan/PLGA nanoparticles on the delivery efficiency of antisense 2'-O-methyl-RNA directed against telomerase in lung cancer cells.

Taetz, S; Nafee, N; Beisner, J; Piotrowska, K; Baldes, C; Mürdter, T E; Huwer, H; Schneider, M; Schaefer, U F; Klotz, U; Lehr, C-M

Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany.

Tailorable cationic chitosan/PLGA nanoparticles (CPNP) were used for the delivery of an antisense 2'-O-methyl-RNA (2OMR) directed against RNA template of human telomerase. Here, we describe the influence of the chitosan content on binding efficiency, complex stability, uptake in different human lung cell types and finally demonstrate the efficacy of this nanoplex system. CPNPs were prepared by the emulsion-solvent evaporation method using different amounts of chitosan and purified by preparative size exclusion chromatography. The characterization by photon correlation spectroscopy and zeta potential measurements showed a small increase in size and an increase of zeta potential with increasing amounts of chitosan. Binding efficiency and complex stability with 2OMR was high in water and correlated well with the chitosan content of particles but was weak in physiologically relevant media (PBS and RPMI cell culture medium). However, flow cytometry analysis showed that the uptake of 2OMR into A549 lung cancer cells was considerably higher in combination with nanoparticles and dependent on the amount of chitosan when compared to 2OMR alone. Confocal laser scanning microscopy revealed that the uptake into A549 cells is mediated via complexes of 2OMR and chitosan/PLGA nanoparticles despite the weak binding in cell culture medium. The nanoparticles were well tolerated and efficient in inhibiting telomerase activity.

PMID: 18703137 [found with GoPubMed]

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