Amphiphilic γ-PGA nanoparticles administered on rat middle ear mucosa produce adjuvant-like immunostimulation in vivo

Abstract

Conclusion: Amphiphilic biodegradable nanoparticles (NPs) composed of poly(γ-glutamic acid) conjugated with L-phenylalanine ethylester (γ-PGA-Phe NPs) applied on the rat middle ear mucosa produce an inflammatory type 1 response. The observation is of relevance for the use of γ-PGA-Phe NPs as a concomitant antigen delivery system and adjuvant measure in the context of vaccinations. Objectives: To examine effects of topical mucosal administration of γ-PGA-Phe NPs as a potentially combined antigen delivery system and adjuvant. Methods: γ-PGA-Phe NPs were administered on rat middle ear mucosa in a sham-controlled design and the response was monitored, focusing on soluble markers in mucosal surface liquids and on overall histopathology. Results: γ-PGA-Phe NPs produced a dose- and time-dependent inflammatory response characterized by generation of proinflammatory cytokines (IL-1α, IL-1β, IL-6, MIP-1α, and TNF-α) and associated histopathological changes.

Keywords::

• Inflammation
• vaccination
• antigen delivery system

Acknowledgments

This work was supported by grants from Vinnova (Multidisciplinary Bio), Lund University (ALF), the Alfred Österlund Foundation, the Japan Science and Technology Agency (Strategic International Cooperative Program and Core Research for Evolutional Science and Technology: CREST), and the Japan Society for the Promotion of Science (Bilateral Joint Research Projects).

Declaration of interest: Except for what is stated in the acknowledgments, the authors declare no financial or other conflicts of interest. The authors alone are responsible for the content and writing of the paper.