Immune response elicited by an intranasally delivered HBsAg low-dose adsorbed to poly-ε-caprolactone based nanoparticles

Int J Pharm. 2016 May 17;504(1-2):59-69. doi: 10.1016/j.ijpharm.2016.03.013. Epub 2016 Mar 11.

Abstract

Among new strategies to increase hepatitis B virus (HBV) vaccination, especially in developing countries, the development of self-administered vaccines is considered one of the most valuable. Nasal vaccination using polymeric nanoparticles (NPs) constitutes a valid approach to this issue. In detail, poly-ε-caprolactone (PCL)/chitosan NPs present advantages as a mucosal vaccine delivery system: the high resistance of PCL against degradation in biological fluids and the mucoadhesive and immunostimulatory properties of chitosan. In vitro studies revealed these NPs were retained in a mucus-secreting pulmonary epithelial cell line and were capable of entering into differentiated epithelial cells. The intranasal (IN) administration of 3 different doses of HBsAg (1.5 μg, 5 μg and 10 μg) adsorbed on a fixed amount of PCL/chitosan NPs (1614 μg) generated identical titers of serum anti-HBsAg IgG and anti-HBsAg sIgA in mice nasal secretions. Besides other factors, the NP surface characteristics, particularly, zeta potential differences among the administered formulations are believed to be implicated in the outcome of the immune response generated.

Keywords: Antigen delivery; Dose-response; Mucosal immunization; Poly-ε-caprolactone (PCL)/chitosan nanoparticles; Polymeric biomaterials; Vaccine adjuvants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / chemistry
  • Administration, Intranasal
  • Adsorption
  • Animals
  • Caco-2 Cells
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chitosan / administration & dosage*
  • Chitosan / chemistry
  • Female
  • Hepatitis B Surface Antigens / administration & dosage*
  • Hepatitis B Surface Antigens / chemistry
  • Hepatitis B Surface Antigens / immunology
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology
  • Immunoglobulin G / blood
  • Mice, Inbred C57BL
  • Mucins / chemistry
  • Mucous Membrane / immunology
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Polyesters / administration & dosage*
  • Polyesters / chemistry
  • Vaccination

Substances

  • Adjuvants, Immunologic
  • Hepatitis B Surface Antigens
  • Immunoglobulin A
  • Immunoglobulin G
  • Mucins
  • Polyesters
  • polycaprolactone
  • Chitosan