Chitosan non-particulate vaccine delivery systems

The development of safe and effective vaccines is a major challenge. In addition to generating an adequate immune response, vaccines must also remain stable over time – both inside and outside the body. In their review article, Masimov and Wasan present various applications of chitosan and chitosan derivatives as adjuvants in the development of particulate and non-particulate vaccines.

Masimov R, Wasan EK. Chitosan non-particulate vaccine delivery systems. J Pharm Pharm Sci. 2024 Jul 24;27:12921. doi: 10.3389/jpps.2024.12921. PMID: 39114808; PMCID: PMC11303186.

In addition to the antigen, adjuvants are also used in vaccine administration to enhance the immune response. Chitosan has immunostimulatory properties, which is why it could play a promising role as an adjuvant in vaccine development. One study, for example, showed that chitosan glutamate as an adjuvant in a polio vaccine significantly increased the immune response.

• Chitosan nanoparticles in vaccines
  Chitosan can be used as a base for nanoparticles o ras a coating for particles with PLGA-based, lipid-based or calcium phosphate-based cores. Various chitosan derivatives such as chitosan HCl, trimethyl chitosan, chitosan glutamate, chitosan glycol or chitosan oligomers are used. These chitosan-based nanoparticles improve the cellular uptake of the vaccine, which is particularly advantageous for mRNA vaccines. They also increase the stability of the particles and promote mucoadhesion, making them suitable for intranasal administration, for example.
• Non-particulate chitosan-based vaccine systems
  In addition to nanoparticles, various non-particulate chitosan systems for vaccine delivery are being researched:
• Microneedles
  Microneedles are micrometer-sized vehicles that are applied to the skin and penetrate the stratum corneum to release the vaccine into the epidermis or dermis. Chitosan and trimethyl chitosan are used to improve efficacy and create a depot effect that allows for prolonged release of the vaccine.
• Hydrogels
  Chitosan-based hydrogels contain the vaccine and provide a controlled release over a longer period of time, which can lead to a stronger immune response. These hydrogels are often temperature-sensitive, so that the vaccine is only released when body temperature is reached.
• Chitosan-antigen conjugates
  By directly covalently linking chitosan to the antigen, the uptake of the antigen is improved. The mucoadhesive properties of chitosan ensure a prolonged residence time at the application site. Furthermore, side effects are reduced.
• Limitations of chitosan-based non-particulate systems
  Although chitosan has promising properties for vaccine delivery, there are also some challenges. Microneedles have a limited loading capacity and cannot be used for all vaccines because some antigens are not compatible due to their charge. In addition, dose fluctuations can occur. For hydrogels, a high salt content can be problematic and there is a risk of a burst release effect, in which the vaccine is released too quickly.

Conclusion: Despite these challenges, chitosan-based vaccine systems show great potential, especially for non-invasive routes of administration. The combination of adjuvant effects, improved stability and targeted drug release makes chitosan a promising material for future vaccine developments.