Preparation of hyaluronic acid-coated polymeric micelles for nasal vaccine delivery

Biomater Sci. 2022 Apr 12;10(8):1920-1928. doi: 10.1039/d1bm01985f.

Abstract

Hyaluronic acid (HA)-coated biodegradable polymeric micelles were developed as nanoparticulate vaccine delivery systems to establish an effective nasal vaccine. We previously reported HA-coated micelles prepared by forming a polyion complex (PIC) of poly(L-lysine)-b-polylactide (PLys+-b-PLA) micelles and HA. The HA-coated micelles exhibited specific accumulation in HA receptor-expressing cells and extremely high colloidal stability under diluted blood conditions. In this study, a model antigen, ovalbumin (OVA), and an adjuvant oligonucleotide containing the CG motif (CpG-DNA) were efficiently loaded in HA-coated micelles via electrostatic interactions. HA-coated micelles delivered OVA and CpG-DNA in mouse bone marrow-derived dendritic cells (BMDCs) and resulted in the upregulation of mRNA encoding IFN-γ and IL-4 in BMDCs. In addition, HA-coated micelles enhanced the expression of the major histocompatibility complex (MHC) class II on BMDCs. We investigated the immune response of HA-coated micelles following intranasal administration. HA-coated micelles induced higher OVA-specific IgG in the blood and OVA-specific IgA in the nasal wash than control (carboxymethyl dextran-coated) micelles. These results suggest that HA-coated micelles efficiently deliver antigens and adjuvants to mucosal-resident immune cells. Therefore, HA-coated micelles are promising platforms for developing nasal vaccines against infectious diseases.

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antigens
  • DNA / pharmacology
  • Dendritic Cells
  • Histocompatibility Antigens Class II
  • Hyaluronic Acid / pharmacology
  • Mice
  • Micelles*
  • Ovalbumin
  • Polymers / pharmacology
  • Vaccines*

Substances

  • Adjuvants, Immunologic
  • Antigens
  • Histocompatibility Antigens Class II
  • Micelles
  • Polymers
  • Vaccines
  • Hyaluronic Acid
  • Ovalbumin
  • DNA