Development of Stabilized Glucomannosylated Chitosan Nanoparticles Using Tandem Crosslinking Method for Oral Vaccine Delivery

Abstract

Aim: The aim of this study was to develop a novel platform technology, comprising of stable glucomannosylated chitosan nanoparticles, for oral immunization. Materials & methods: Chitosan nanoparticles were stabilized by tandem crosslinking using tripolyphosphate followed by glutaraldehyde. Process and formulation variables were optimized using a ‘Box–Behnken’ design. The in vitro and in vivo performances were established in RAW 264.7 and BALB/c mice, respectively. Results: The lyophilized formulation was exceptionally stable in simulated biological media and the enclosed antigen was conformationally stable. The mechanistic understanding of glucomannosylated chitosan nanoparticles in RAW 264.7 revealed transcellular uptake via both mannose and glucose transporter-mediated endocytosis. Glucomannan modification resulted in significantly higher systemic (serum IgG titer), mucosal (secretory IgA) and cell-mediated (IL-2 and IFN-γ) immune responses in comparison with nonmodified chitosan nanoparticles. Conclusion: The present strategy is expected to contribute some novel tools for the oral delivery of numerous biomacromolecules.

Keywords::

• APC
• chitosan
• glucomannan
• nanoparticle
• oral immunization

Supplementary Material

Financial & competing interests disclosure

This project work was financially supported by the Department of Biotechnology of the Government of India (New Delhi, India). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

Authors are thankful to the Director of the National Institute of Pharmaceutical Education and Research (Punjab, India) for providing necessary infrastructure facilities. Technical assistance provided by Rahul Mahajan is also duly acknowledged.

Additional information

Funding

This project work was financially supported by the Department of Biotechnology of the Government of India (New Delhi, India). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.