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Significant systemic and mucosal immune response induced on oral delivery of diphtheria toxoid using nano‐bilosomes
Author(s) -
Shukla Anshuman,
Singh Bhupinder,
Katare O P
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01452.x
Subject(s) - diphtheria toxin , toxoid , diphtheria , alum , immune system , antibody , immunology , antigen , immunization , in vivo , medicine , chemistry , pharmacology , toxin , vaccination , biology , biochemistry , microbiology and biotechnology , organic chemistry
BACKGROUND AND PURPOSE Over the last decade apprehension has been growing over the effectiveness of existing parenteral vaccines for diphtheria and has created an interest in the development of a mucosally active vaccine. Oral immunization appears to be an effective alternative, but is not without the inherent disadvantages of antigen destruction and tolerance. Therefore, our objective was to investigate the incorporation of diphtheria toxoid (DTx) into bilosomes, which could provide protection as well as aid transmucosal uptake and subsequent immunization. Another objective was to determine the oral dose that will produce serum antibody titres comparable with those produced by i.m. doses of DTx. EXPERIMENTAL APPROACH Bilosomes containing DTx were prepared by thin film hydration and characterized in vitro for their shape, size, percent antigen entrapment and stability. In the in vivo study the anti‐DTx IgG and anti‐DTx sIgA response was estimated using elisa , in serum and in various body secretions, respectively, following oral immunization with different doses of DTx entrapped in nano‐bilosomes. KEY RESULTS High dose loaded nano‐bilosomes (DTxNB3, 2Lf) produced comparable anti‐DTx IgG levels in serum to those induced by i.m. alum‐adsorbed DTx (0.5Lf). In addition, all the nano‐bilosomal preparations elicited a measurable anti‐DTx sIgA response in mucosal secretion, whereas i.m. alum‐adsorbed DTx (0.5Lf) was unable to elicit this response. CONCLUSIONS AND IMPLICATIONS The orally administered nano‐bilosomal DTx formulation produced comparable serum antibody titres to i.m.alum‐adsorbed DTx, at a fourfold higher dose and without the induction of tolerance. This approach will provide an effective and comprehensive immune protection against diphtheria with better patient compliance.