title: Improved stability and immunological potential of tetanus toxoid containing surface engineered bilosomes following oral administration.
abstract: The present study was designed with the objective to investigate the stability and potential of glucomannan-modified bilosomes (GM-bilosomes) in eliciting immune response following oral administration. GM-bilosomes exhibited desired quality attributes simultaneously maintaining the chemical and conformation stability of the tetanus toxoid (TT) entrapped in to freeze dried formulations. The GM-bilosomes exhibited excellent stability in different simulated biological fluids and sustained release profile up to 24 h. GM-bilosomes elicited significantly higher (P<0.05) systemic immune response (serum IgG level) as compared to bilosomes, niosomes and alum adsorbed TT administered through oral route. More importantly, GM-bilosomes were found capable of inducing mucosal immune response, i.e. sIgA titre in salivary and intestinal secretions as well as cell mediated immune response (IL-2 and IFN-γ levels in spleen homogenate) which was not induced by i.m. TT, the conventional route of immunization. Conclusively, GM-bilosomes could be considered as a promising carrier and adjuvant system for oral mucosal immunization.
  
  
  BACKGROUND
  This team reports on the development and effects of a glucomannan-modified bilosome as an oral vaccine vector, using tetanus toxoid in the experiments. These GM-bilosomes not only elicited significantly higher systemic immune response as compared to bilosomes, niosomes and alum adsorbed orally administered TT, but also demonstrated mucosal immune response induction as well as cell mediated immune responses, which were not induced by the conventional route of immunization.
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali) Punjab India. Electronic address: sanyogjain@niper.ac.in.
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali) Punjab India.
authors.forename: Harshad
authors.initials: H
authors.lastname: Harde
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali) Punjab India.
authors.forename: Anura
authors.initials: A
authors.lastname: Indulkar
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali) Punjab India.
authors.forename: Ashish Kumar
authors.initials: AK
authors.lastname: Agrawal
mesh_terms: D000284:Administration, Oral; D000327:Adsorption; D000818:Animals; D002460:Cell Line; D004337:Drug Carriers; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008351:Mannans / Q000737:chemistry; D008358:Mannose / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa / Q000187:drug effects; D050997:Nanomedicine; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011487:Protein Conformation; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013499:Surface Properties; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D004337:Drug Carriers; D007376:Interleukin-2; D008081:Liposomes; D008351:Mannans; D010714:Phosphatidylethanolamines; D011108:Polymers; D013745:Tetanus Toxoid; D012710:Serum Albumin, Bovine; C022901:(1-6)-alpha-glucomannan; D007371:Interferon-gamma; D008358:Mannose
keywords: Bilosomes; Mannosylation; Oral immunization; Tetanus toxoid; Vaccine delivery