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Fabrication and characterization of DDAB/PLA-alginate composite microcapsules as single-shot vaccine

Yang, Meiyang, Yang, Tingyuan, Jia, Jilei, Lu, Ting, Wang, Hailin, Yan, Xueying, Wang, Lianyan, Yu, Lian, Zhao, Yue
RSC advances 2018 v.8 no.24 pp. 13612-13624
alginates, cell-mediated immunity, chronic hepatitis B, compliance, cytokines, developing countries, encapsulation, gels, hepatitis B antigens, immune response, immunoglobulin G, microparticles, nanoparticles, particle size, phosphates, polylactic acid, quaternary ammonium compounds, response surface methodology, secretion, sodium chloride, toxicity, vaccination, vaccines
The most effective method to reduce chronic hepatitis B virus infection is the universal implementation of vaccination. The commercial aluminum-based vaccines need multiple-injection protocols for complete protection resulting in poor compliance in developing countries. It is necessary to develop single-shot vaccine formulations. In this study, novel antigen-loaded DDAB/PLA (didodecyldimethylammonium bromide/poly(lactic acid)) nanoparticles (NPs)-alginate composite microcapsules were developed as a single-shot vaccine. The hepatitis B surface antigen (HBsAg)-loaded DDAB/PLA NPs were successfully encapsulated into alginate microcapsules by a modified spray-solidification technique. The response surface method was applied to optimize the preparation parameters employing encapsulation efficiency of HBsAg and particle size of microcapsules as response variables. The antigen-loaded DDAB/PLA NPs-alginate composite microcapsules were prepared under these optimal conditions: the size of composite microcapsules was 24.25 μm, the Span value was 1.627, and the encapsulation efficiency of HBsAg was 68.4%. The obtained microcapsules were spherical gel microparticles with excellent dispersity and narrow size distributions. In vitro release profile indicated a slow release rate of encapsulated HBsAg especially in phosphate buffered saline solution. The microcapsules showed little toxicity in vivo. This vaccine delivery system could induce stronger immune responses by a single shot, which exhibited much higher cytokine secretion levels closely related to cellular immunity and comparable IgG titers to the traditional aluminum-adjuvanted vaccine with three shots.