title: Enhanced mucosal immune responses against tetanus toxoid using novel delivery system comprised of chitosan-functionalized gold nanoparticles and botanical adjuvant: characterization, immunogenicity, and stability assessment.
abstract: Approaches based on combined use of delivery systems and adjuvants are being favored to maximize efficient mucosal delivery of antigens. Here, we describe a novel delivery system comprised of chitosan-functionalized gold nanoparticles (CsAuNPs) and saponin-containing botanical adjuvant; Asparagus racemosus extract (ARE) for oral delivery of tetanus toxoid (TT). A significant increase in TT-specific IgG (34.53-fold) and IgA (43.75-fold) was observed when TT-CsAuNPs were formulated with ARE (TT-ARE-CsAuNPs). The local IgA immune responses for TT also showed a significant increase (106.5-fold in intestine washes and 99.74-fold in feces) with ARE-based formulations as compared with plain TT group. No effect of ARE was observed on size, charge, and loading properties of CsAuNPs. Additionally, no effect of ARE and CsAuNPs was observed on antigenicity and secondary structure of TT as determined by fluorescence, circular dichroism, and Fourier transform infrared spectroscopy. The stability studies demonstrated excellent stability profile of formulation at recommended storage conditions. The study establishes the possible role of immunomodulatory adjuvants in particulate delivery systems for mucosal delivery of vaccines.
authors.affiliation: Department of Pharmaceutics, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune 411038, India; Serum Institute of India Ltd., 212/2, Hadapsar, Pune 411028, India.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Barhate
authors.affiliation: Serum Institute of India Ltd., 212/2, Hadapsar, Pune 411028, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Gautam
authors.affiliation: Serum Institute of India Ltd., 212/2, Hadapsar, Pune 411028, India.
authors.forename: Sunil
authors.initials: S
authors.lastname: Gairola
authors.affiliation: Serum Institute of India Ltd., 212/2, Hadapsar, Pune 411028, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Jadhav
authors.affiliation: Department of Pharmaceutics, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune 411038, India. Electronic address: vbpokharkar@yahoo.co.in.
authors.forename: Varsha
authors.initials: V
authors.lastname: Pokharkar
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D027761:Asparagus Plant / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D002942:Circular Dichroism; D004337:Drug Carriers; D004355:Drug Stability; D004356:Drug Storage; D006046:Gold / Q000737:chemistry*; D018928:Immunity, Mucosal / Q000187:drug effects*; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D053768:Metal Nanoparticles; D051379:Mice; D009061:Mouth Mucosa / Q000187:drug effects* / Q000276:immunology; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D012503:Saponins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D004337:Drug Carriers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010936:Plant Extracts; D012503:Saponins; D013745:Tetanus Toxoid; D006046:Gold; D048271:Chitosan
keywords: Asparagus racemosus; Chitosan; Gold nanoparticle; Immunology; In vitro/in vivo correlations (IVIVC); Physical characterization; Transmucosal drug delivery; Vaccine adjuvant; Vaccine delivery systems