Evaluation of effectiveness of polymeric nanoparticles based vaccine delivery system over varying time intervals using tetanus toxoid as model antigen

Abstract

At present choice of adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable level of side-effects. To overcome the side effects, encapsulation of antigen in the biodegradable polymeric nanoparticles (NPs) may be a promising approach, which may be developed as adjuvants. Moreover, small size of these nano-formulations may help to project the antigen directly to the antigen presenting cells (APCs) for stimulating cell mediate immunity. The present study was directed towards the evaluation of PLA and PCL based nanoformulations as potential adjuvants by using tetanus toxoid as model antigen. The particles size was observed in the range from 92.9 ± 2.6 to 124.6 ± 3.7 nm having zeta potential of -12.4 ± 1.2 to -3.4 ± 1.5. The loading efficiency of different formulations ranges from 46.3 - 56.8 %. Highest loading of 56.8% and burst release (82 % in 48 days) was observed in PLA-PEG based nanoformulation. In terms of anti-tetanus antibodies (determined by ELISA) titer of > 0.5 IU/ml was observed upto 70 days in all the survived mice. Efficacy of nanoformulations was studied in mice by challenge method over different time intervals wherein tetanus loaded PLA, PLA-PEG and PCL NPs shows maximum efficacy at 28, 56 and 21 days respectively. The study shows that the biodegradable nanoparticle based formulations has no toxicity, comparable efficacy and therefore has a strong potential as vaccine adjuvant and delivery system.