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Microfluidics for the production of chitosan-TPP nanoparticles

Microfluidics can precisely control the physiochemical properties of nanoparticles by mixing to the nanoliter. For this reason, nanoparticles for the transport of peptide drugs are to be developed in the study presented here with the help of chitosan from Heppe Medical Chitosan GmbH.



Non-invasive peptides delivery using chitosan nanoparticles assembled via scalable microfluidic technology

Giorgia Maurizii, Sofia Moroni, Javier Vicente Jimènez Núnez, Giulia Curzi, Mattia Tiboni, Annalisa Aluigi, Luca Casettari, Non-invasive peptides delivery using chitosan nanoparticles assembled via scalable microfluidic technology, Carbohydrate Polymer Technologies and Applications, Volume 7, 2024, 100424, ISSN 2666-8939,

Peptide drugs offer a promising alternative to small molecule drugs due to their high selectivity, efficacy and low toxicity. However, peptide drugs can currently only be administered intravenously. In order to enable non-invasive routes of administration, such as nasal, oral or pulmonary, suitable drug delivery systems must be developed. Polymer-based nanoparticles are particularly promising. They have many advantages, e.g. good protection against premature degradation of the active ingredient, more targeted transport, as well as improved bioavailability and intracellular penetration.

Chitosan stands out as a material for this, as it also has good biocompatibility, biodegradability, antibacterial and antioxidant properties. Ionotrophic gelation is the most common method for producing chitosan nanoparticles. Here, the positively charged chitosan is mixed with another, negatively charged molecule such as tripolyphosphate (TPP) and forms nanoparticles through a sol-gel transition. The conventional bulk method often results in high batch-to-batch variations. This could be avoided by using microfluidic chips. The physiochemical properties of the nanoparticles can be controlled through the miniaturization of the manufacturing process and the possibility of adding liquids in the nanolitre range. In addition, manufacturing in microfluidic chips has the advantage that nanoparticle properties can be optimized by microfluidic parameters such as the total flow rate, the ratio of the flows to each other and the chip geometry, and the scale-up is simplified.

In the study presented here, a self-made 3D microfluidic chip will be used for the production of chitosan TPP nanoparticles loaded with argireline as a model cargo. The aim is to develop a suitable transporter for peptide drugs by varying the flow rate in the chip, the pH and the concentration of the chitosan. A chitosan with the specification 80/20 from Heppe Medical Chitosan GmbH is used in the study. The nanoparticles were then embedded in a gel matrix to enable topical application.


  • Chitosan concentration and pH have the greatest influence on particle size, while chitosan and TPP concentrations influence PDI → Best nanoparticle properties at pH 5, 2 mg/ml chitosan and 0.5 mg/ml TPP
  • Entrapment efficiency of 90 % of argireline for the selected nanoparticle composition and a size of 186.0 ± 1.0 nm and a PDI of 0.440 ± 0.002
  • Nanoparticles in gel matrix possessed suitable mechanical properties (e.g. hardness, compressibility, adhesiveness, cohesion and elasticity) for transdermal delivery of argireline
  • Improved drug release over 48 h compared to free nanoparticles

Conclusions: This study has demonstrated that the microfluidic-assisted ionotropic gelation method could be an easily scalable platform for the preparation of peptide-loaded CS-TPP NPs that could potentially be used for the transdermal delivery of biologics.

Link to article:

drug delivery, chitosan, chitosan by HMC, microfluidic, chitosan nanoparticles, peptids

Congress and fairs

Meet us in person 2024:

  • 14th PBP World Meeting/ Research Pharm, Vienna, Austria, 18.-21.03.2024
  • EPNOE Workshop on Analytics of Polysaccharides, ETH Zürich, Zürich, Switzerland, 25.-26.06.2024
  • CPHI, Milan, Italy, 08.-10.10.2024
  • MEDICA 2024, Düsseldorf, Germany, 11.-14.11.2024

To arrange an appointment please contact Katja Richter via This email address is being protected from spambots. You need JavaScript enabled to view it.


  • Heppe Medical Chitosan GmbH
    Heinrich-Damerow-Strasse 1
    06120 Halle (Saale)
  • Tel.: +49 (0) 345 27 996 300
    Fax: +49 (0) 345 27 996 378
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