title: Development and characterization of surface modified PLGA nanoparticles for nasal vaccine delivery: effect of mucoadhesive coating on antigen uptake and immune adjuvant activity.
abstract: In this study, the efficacy of mucoadhesive polymers, i.e., chitosan and glycol chitosan as a mucoadhesive coating material in nasal vaccine delivery was investigated. The Hepatitis B surface Antigen (HBsAg) encapsulated PLGA, chitosan coated PLGA (C-PLGA), and Glycol chitosan coated PLGA (GC-PLGA) nanoparticles (NPs) were prepared. The formulations were characterized for particle size, shape, surface charge, and entrapment efficiency. The mucoadhesive ability of coated and non-coated NPs was determined using in vitro mucoadhesion and nasal clearance test. In addition, the systemic uptake and bio-distribution were also evaluated to understand the fate of NPs following nasal delivery. The immuno-adjuvant ability of various formulations was compared by measuring specific antibody titer in serum and secretory. The results indicated that PLGA NPs exhibit negative surface charge, whereas C-PLGA and GC-PLGA NPs exhibited positive surface charge. The GC-PLGA NPs demonstrated lower clearance and better local and systemic uptake compared to chitosan coated and uncoated PLGA NPs. In vivo immunogenicity studies indicated that GC-PLGA NPs could induce significantly higher systemic and mucosal immune response compared to PLGA and C-PLGA NPs. In conclusion, GC-PLGA NPs could be a promising carrier adjuvant for the nasal vaccine delivery for inducing a potent immune response at mucosal surface(s) and systemic circulation.
authors.affiliation: Department of Pharmaceutical Sciences, Jawaharlal Nehru Technical University, Hyderabad, India; Research and Development, Shantha Biotechnics Limited (A Sanofi Company), Hyderabad, India.
authors.forename: Dilip
authors.initials: D
authors.lastname: Pawar
authors.forename: Sharad
authors.initials: S
authors.lastname: Mangal
authors.forename: Roshan
authors.initials: R
authors.lastname: Goswami
authors.forename: K S
authors.initials: KS
authors.lastname: Jaganathan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D048271:Chitosan / Q000737:chemistry; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D006801:Humans; D018928:Immunity, Mucosal; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D014018:Tissue Distribution
chemical_list: D000276:Adjuvants, Immunologic; D005079:Excipients; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; C118638:glycol-chitosan; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan
keywords: Drug Delivery; Glycol chitosan; Hepatitis B surface antigen; Mucosal immunization; PLGA nanoparticles; Single shot vaccine