Hemostatic effect of chitosan and stability of chitosan hydrogels
Chitosan and chitosan derivatives have different properties due to molecular parameters, such as degree of deacetylation and molecular weight. In this article, we present a paper that examined the effect of these parameters on the hemostatic effect of chitosan. Another topic is the long-term stability of chitosan hydrogels according to ICH guidelines.
Investigation of the Effects of Molecular Parameters on the Hemostatic Properties of Chitosan
Zhang Hu, Sitong Lu, Yu Cheng, Songzhi Kong, Sidong Li, Chengpeng Li, Lei Yang. Molecules 2018, 23(12), 3147; doi:10.3390/molecules23123147
Hemorrhea can be life-threatening for the patient in war, trauma car, or surgical procedures. The biopolymer chitosan has already been used in various forms for hemostasis in recent years. In the study, chitosans with different properties (degree of deacetylation, molecular weight, derivatives with different degrees of substitution) were prepared from chitin. The haemostatic effect of the chitosans prepared was compared on the basis of clotting time and a dynamic coagulation assay in vitro. The structure-activity relationship and the mechanism of chitosan hemostasis were investigated. The following chitosans were compared.
| Chitosan with different molecular parameters | DDA (%) | MW (kDa) | |
| Chitosan | Different DDA | 53 | 1010 |
| 68 | 933 | ||
| 82 | 891 | ||
| 92 | 877 | ||
| Chitosan | Different MW | 82 | 485 |
| 82 | 212 | ||
| 82 | 56 | ||
| 82 | 27 | ||
| Chitosan Derivatives | N-Acetyl-chitosan | ||
| O-carboxylmethyl-chitosan | |||
| O-hydroxypropyl-chitosan | |||
| Chitosan-HI | |||
| Chitosan-acetate | |||
| Chitosan-lactate | |||
| Chitosan-Gentisic acid | |||
Table 1: Chitosans with different molecular parameters. DDA: degree of deacetylation; MW: molecular weight
Results:
- positively charged chitosan initiates aggregation of negatively charged red blood cells
- average coagulation time between 563 to 1025s
- shortest coagulation time for a DDA of 68%
- better coagulation effect with greater MW at similar DDA
- Chitosan lactate showed strong procoagulant properties
- Chitosans with different molecular properties may not trigger blood clotting via the same mechanism
Conclusion: The authors showed that the molecular properties of produced chitosans and chitosan derivatives influence their hemostatic effects. How the structure of chitosan is related to its blood coagulation properties requires further research.
Source: https://www.mdpi.com/1420-3049/23/12/3147
Comparison of Rheological, Drug Release, and Mucoadhesive Characteristics upon Storage between Hydrogels with Unmodified or Beta-Glycerophosphate-Crosslinked Chitosan.
E. Szymańska, A. Czajkowska-Kośnik, K. Winnicka International Journal of Polymer Science Volume 2018, https://doi.org/10.1155/2018/3592843
Chitosan is used as an adjuvant for a wide range of pharmaceutical applications such as drug delivery, wound dressings, vaccines and scaffolds for tissue regeneration. A challenge for development of chitosan-based medical devices is the limited long-term stability. In order to increase the stability of chitosan systems, chemical crosslinking is usually performed. In the present study, long-term stability of beta-glycerophosphate-crosslinked chitosan hydrogels was investigated in comparison to unmodified chitosan hydrogels. Chitosan 80/500 (degree of deacetylation [%]/ viscosity of 1% chitosan solution in 1% acetic acid [mPa·s]) by HMC was used to prepare 3 and 4% chitosan hydrogels. The ratio of chitosan to acetic acid was 0.6:1.0. The following table gives an overview of the storage conditions and test intervals according to ICH guideline.
| Stability studies | Storage conditions | Time (month) | Testing intervals (month) |
| Long-term |
25°C±2°C 60±6% RH |
12 | 1, 3, 6, 12 |
| 4±2°C | 6 | 1, 3, 6 | |
| Accelerated |
40±2°C 75±5% RH |
6 | 1,3,6 |
Table 2: Storage conditions and time intervals applied for the stability studie. RH: relative humidity
The chitosan hydrogels were tested for macroscopic appearance, pH and viscosity at indicated times. In addition, drug content, particles size and release in vitro as well as mechanical and mucoadhesive (ex vivo) properties of the gel were characterized.
Results:
Unmodified chitosan hydrogels
- Change of color, loss of gel structure and homogeneity after 3 months storage at 25°C
- Only at 4±2°C no change in appearance after 3 month
- Viscosity decreased over time for all storage conditions due to depolymerization induced by the high acid concentration and warming
- Reduction by 40% at 4±2°C, 50% at 25°C/60%RH and 90% at 40°C/75%RH after 3 month of storage
- After 6 month, viscosity was reduced by 60% at 4±2°C and 70% at 25°C/60%RH
Crosslinked chitosan hydrogels:
- Stabilization by crosslinking, especially at refrigerated storage
- 4°C±2: Stable viscosity after 3 month, reduction of viscosity (25%) after 6 month
- Ambient: slight decrease after 3 month, significant drop in viscosity (40%) after 6 month
- Accelerated: Increase in viscosity
- Preserved rheological and mucoadhesive behavior at 4 ± 2°C
- Drug content stable for all tested conditions
- Changes in viscosity affected mucoadhesive properties and drug release rates of the hydrogel
Conclusion: The stability study compared unmodified and crosslinked chitosan hydrogels and showed the stabilizing effect of cross-linking under refrigerated conditions. Organoleptic and rheological behavior as well as hydrogel structure were preserved during storage of 3-month.