title: Divalent toxoids loaded stable chitosan-glucomannan nanoassemblies for efficient systemic, mucosal and cellular immunostimulatory response following oral administration.
abstract: The present study reports dual tetanus and diphtheria toxoids loaded stable chitosan-glucomannan nanoassemblies (sCh-GM-NAs) formulated using tandem ionic gelation technique for oral mucosal immunization. The stable, lyophilized sCh-GM-NAs exhibited ~152 nm particle size and ~85% EE of both the toxoids. The lyophilized sCh-GM-NAs displayed excellent stability in biomimetic media and preserved chemical, conformation and biological stability of encapsulated toxoids. The higher intracellular APCs uptake of sCh-GM-NAs was concentration and time dependent which may be attributed to the receptor mediated endocytosis via mannose and glucose receptor. The higher Caco-2 uptake of sCh-GM-NAs was further confirmed by ex vivo intestinal uptake studies. The in vivo evaluation revealed that sCh-GM-NAs posed significantly (p<0.001) higher humoral, mucosal and cellular immune response than other counterparts by eliciting complete protective levels of anti-TT and anti-DT (~0.1 IU/mL) antibodies. Importantly, commercial 'Dual antigen' vaccine administered through oral or intramuscular route was unable to elicit all type of immune response. Conclusively, sCh-GM-NAs could be considered as promising vaccine adjuvant for oral mucosal immunization.
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab 160062, 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, SAS Nagar, Punjab 160062, India.
authors.forename: Krupa
authors.initials: K
authors.lastname: Siddhapura
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab 160062, India.
authors.forename: Ashish Kumar
authors.initials: AK
authors.lastname: Agrawal
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab 160062, India. Electronic address: sanyogjain@niper.ac.in.
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry*; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D004339:Drug Compounding; D005612:Freeze Drying; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D018928:Immunity, Mucosal / Q000187:drug effects; D007114:Immunization / Q000379:methods; D007408:Intestinal Absorption; D008351:Mannans / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D014121:Toxoids / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D004168:Diphtheria Toxoid; D008351:Mannans; D013745:Tetanus Toxoid; D014121:Toxoids; C022901:(1-6)-alpha-glucomannan; D048271:Chitosan
keywords: Chitosan-glucomannan nanoassemblies; Glucomannosylation; Mucosal immunity; Stability; Vaccine