M-cell targeted delivery of recombinant hepatitis B surface antigen using cholera toxin B subunit conjugated bilosomes

Int J Pharm. 2010 Jan 29;385(1-2):47-52. doi: 10.1016/j.ijpharm.2009.10.027. Epub 2009 Oct 14.

Abstract

The present study aims to improve upon our earlier findings with bilosomes as potential delivery vehicle through oral route for recombinant hepatitis B surface antigen (HBsAg). The work entails the conjugation of bilosomal system with cholera toxin B subunit (CTB) to increase transmucosal uptake via M-cell specific delivery approach. The study encompasses the development and characterization of HBsAg-loaded CTB-conjugated system for percent antigen entrapment, size, shape, and stability in SGF (USP, pH 1.2), SIF (USP, pH 7.5) and in bile salt solutions. Biological activity of CTB, subsequent to conjugation, was verified by hemagglutination test. Anti-HBsAg IgG response in serum and anti-HBsAg sIgA in various body secretions were estimated using ELISA, following oral immunization with 10 microg dose-loaded CTB-conjugated bilosomes (CTB2) and 20 microg dose-loaded CTB-conjugated bilosomes (CTB1) in BALB/c mice. The results showed that CTB1 produced anti-HBsAg IgG antibody titre response comparable to that of the intramuscular (i.m.) injection of 10 microg of alum-adsorbed HBsAg. Moreover, all the bilosomal preparations elicited measurable sIgA vis-à-vis negligible response with i.m. administered HBsAg. Thus, HBsAg-loaded CTB-conjugated bilosomes provide a promising potential for targeted oral immunization against hepatitis B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Bile Acids and Salts / chemistry*
  • Chemistry, Pharmaceutical
  • Cholera Toxin / administration & dosage*
  • Cholera Toxin / chemistry
  • Cholera Toxin / immunology
  • Drug Carriers*
  • Drug Stability
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hepatitis B Antibodies / blood
  • Hepatitis B Surface Antigens / administration & dosage*
  • Hepatitis B Surface Antigens / chemistry
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B Vaccines / administration & dosage*
  • Hepatitis B Vaccines / chemistry
  • Hepatitis B Vaccines / immunology
  • Hexoses / chemistry
  • Immunity, Mucosal
  • Immunotoxins / administration & dosage*
  • Immunotoxins / chemistry
  • Immunotoxins / immunology
  • Injections, Intramuscular
  • Intestinal Mucosa / immunology
  • Lipids / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Fluorescence
  • Particle Size
  • Peyer's Patches / cytology
  • Peyer's Patches / immunology*
  • Recombinant Proteins
  • Stearates / chemistry

Substances

  • Bile Acids and Salts
  • Drug Carriers
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Hexoses
  • Immunotoxins
  • Lipids
  • Recombinant Proteins
  • Stearates
  • sorbitan tristearate
  • Cholera Toxin