In vivo efficacy and toxicity evaluation of polycaprolactone nanoparticles and aluminum based admixture formulation as vaccine delivery system
2015
Delivery of antigen through admixture formulation containing poly caprolactone (PCL) and aluminum phosphate was studied as a promising strategy to generate antigen specific immune response. The present study demonstrates the synergistic effect of admixture formulation of PCL with reduced aluminum (PCL-Al 0.2mg-TT and PCL-PEG-Al 0.2mg-TT) as a potential adjuvant system using tetanus toxoid (TT) as a model antigen. On evaluation of the magnitude of efficacy for the proposed formulation by ELISA as well as challenge method, persistent and strong antibody response was obtained throughout the 180 day study period on storage at 5±3°C. In comparison to the aluminum phosphate based conventional tetanus vaccine, higher levels of IFN-γ and IL-4 were obtained with PCL-Al 0.2mg-TT and PCL-PEG-Al 0.2mg-TT, indicating the presence of cell mediated as well as humoral immune responses. Histopathology and serum biochemistry profile in mice further indicated the suitability of the proposed formulation. Percent adsorption/encapsulation of the antigen also increased to nearly 95% in the admixture formulation compared to 55% adsorption in the conventional tetanus vaccine. The present study established a useful baseline for designing biocompatible and effective delivery system for toxoid vaccines through judicious use of PCL based biodegradable nanoparticles in combination with aluminum phosphate.
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