Mucoadhesive glycol chitosan nanoparticles for intranasal delivery of hepatitis B vaccine: enhancement of mucosal and systemic immune response.
In this study, for the first time, glycol chitosan (GC) nanoparticles (NPs) were prepared and evaluated to obtain systemic and mucosal immune responses against nasally administered hepatitis B surface antigen (HBsAg). Size, zeta potential and morphology of the NPs were investigated as a function of preparation method. NPs with high loading efficacy ( > 95%) and positively charged surface were obtained with an average particle size of approximately 200 nm. The structural integrity of HBsAg in NPs was evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis and further confirmed by measuring the in vitro antigenicity using an enzyme immunoassay. During in vivo studies, GC NPs showed the lowest nasal clearance rate and better mucosal uptake when compared with chitosan (CS) NPs. The immunogenicity of NPs-based delivery system(s) was assessed by measuring anti-HBsAg antibody titer in mice serum and secretions after intranasal administration. The alum-based HBsAg vaccine injected subcutaneously was used as positive control. Results indicated that alum-based HBsAg induced strong humoral but negligible mucosal immunity. However, GC NPs induced stronger immune response at both of the fronts as compared to generated by CS NPs. This study demonstrates that this newly developed system has potential for mucosal administration of vaccines.
a Department of Pharmaceutical Sciences , Jawaharlal Nehru Technical University , Hyderabad , Andhra Pradesh , India and.|b Research and Development , Shantha Biotechnics Limited (A Sanofi Company) , Medchal , Hyderabad , Andhra Pradesh , India.
Dilip
D
Pawar
b Research and Development , Shantha Biotechnics Limited (A Sanofi Company) , Medchal , Hyderabad , Andhra Pradesh , India.
K S
KS
Jaganathan
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D016503:Drug Delivery Systems; D005260:Female; D006508:Hepatitis Antibodies / Q000032:analysis / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage* / Q000494:pharmacology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000494:pharmacology*; D007109:Immunity / Q000187:drug effects*; D018928:Immunity, Mucosal / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D011817:Rabbits; D012995:Solubility; D014014:Tissue Adhesives
D000276:Adjuvants, Immunologic; D006508:Hepatitis Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D014014:Tissue Adhesives; C118638:glycol-chitosan; D048271:Chitosan
Glycol chitosan; hepatitis B surface antigen; mucosal immunization; nanoparticles; vaccine