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

Acta Otolaryngol. 2014 Oct;134(10):1034-41. doi: 10.3109/00016489.2014.918278.

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; antigen delivery system; vaccination.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Administration, Topical
  • Animals
  • Biomarkers / analysis
  • Cytokines / analysis
  • Disease Models, Animal
  • Ear, Middle / drug effects*
  • Ear, Middle / immunology
  • Ear, Middle / pathology
  • Immunization / methods*
  • Immunohistochemistry
  • Male
  • Mucous Membrane / drug effects
  • Mucous Membrane / pathology
  • Nanoparticles / administration & dosage
  • Polyglutamic Acid / analogs & derivatives*
  • Polyglutamic Acid / immunology
  • Polyglutamic Acid / pharmacology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Sensitivity and Specificity
  • Surface-Active Agents / pharmacology

Substances

  • Adjuvants, Immunologic
  • Biomarkers
  • Cytokines
  • Surface-Active Agents
  • poly(gamma-glutamic acid)
  • Polyglutamic Acid