Synthesis, characterization and evaluation of novel triblock copolymer based nanoparticles for vaccine delivery against hepatitis B.
Poly lactic acid (PLA) is one of widely used biodegradable polymer in vaccine delivery. However, the use is restricted due to hydrophobic nature and generation of acidic microenvironment upon its degradation, rendering it unfavorable to the encapsulated antigen. In the present study we have synthesized PEG derivatized block copolymers of PLA for development of nanoparticles encapsulating HBsAg for mucosal vaccination against hepatitis B. The copolymers of compositions AB, ABA and BAB (PLA as A-block and PEG as B-block) were synthesized and characterized by 1H NMR spectroscopy and gel permeation chromatography. Nanoparticles were characterized to determine the effect of copolymer. Among all, BAB produced nanoparticles of smallest size and lowest zeta potential, suggesting highest PEG density on their surface. The in vitro release experiments were performed in PBS (pH7.4). SDS-PAGE analysis confirmed the structural stability and integrity of the released antigen. Results were compared for immunogenicity with plain PLA nanoparticles and conventional alum-HBsAg based vaccine. BAB nanoparticles produced better humoral response as compared to other polymeric nanoparticles. The extent of humoral response obtained in single dose of BAB nanoparticles was comparable to the response produced by alum based vaccine (which received a booster dose). Block copolymeric nanoparticles also produced better sIgA level at all local and distal mucosal sites as compare of PLA nanoparticles, where alum based formulation failed to give any considerable response. Additionally, IgG1 and IgG2a isotype were determined to confirm the T(H)1/T(H)2 mixed immune response. These data demonstrate the potential of BAB nanoparticles as mucosal vaccine delivery system capable of eliciting high and prolonged immune response.
Jain
Arvind K
AK
Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Vishwavidyalaya Sagar (M. P.) 470003, India.
Goyal
Amit K
AK
Gupta
Prem N
PN
Khatri
Kapil
K
Mishra
Neeraj
N
Mehta
Abhinav
A
Mangal
Sharad
S
Vyas
Suresh P
SP
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006509:Hepatitis B / Q000517:prevention & control*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000138:chemical synthesis; D019344:Lactic Acid / Q000008:administration & dosage* / Q000138:chemical synthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011091:Polyesters; D011108:Polymers / Q000008:administration & dosage* / Q000138:chemical synthesis
D017325:Hepatitis B Vaccines; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)