Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi 221005, India.
Department of Anaesthesia and Critical Care, Sanjay Gandhi Memorial Hospital, Delhi 110005, India.
Int J Biol Macromol. 2018 May;111:804-812. doi: 10.1016/j.ijbiomac.2018.01.073. Epub 2018 Jan 16.
The present work is focused on the development and evaluation of single dose sustained-release Hepatitis B surface antigen (HBsAg) loaded nanovaccine for Hepatitis B. The conventional treatment suffers from repeated administration and hence requires a booster dose. Therefore, polymeric nanovaccine of HBsAg was developed by double emulsion solvent evaporation technique, utilizing central composite design for formulation optimization. The effects of independent variables (like polymer amount, stabilizer concentration, aqueous/organic phase ratio and homogenizer speed) were also studied on critical quality attributes like particle size and entrapment efficiency. Nanovaccine was characterized in terms of physicochemical parameters, release, internalization and in vivo immunological evaluation in BALB/c mice after administration by different routes such as oral, sub-cutaneous, nasal and intramuscular. The designed nanovaccine demonstrated nanometric size with smooth surface, negative zeta potential, maximum entrapment, sustained release and better internalization in macrophage and MRC-5 cell line. The immune-stimulating activity of nanovaccine administered by different routes was evaluated by measuring anti-HBsAg titre like specific immunoglobulin IgG and IgA response and cytokine level (interleukin-2, interferon-Y) measurement. The results indicated that the nanovaccine administered by intramuscular route produced better humoral as well as cellular responses and potential carriers for antigen delivery at single dose administration via intramuscular route.
本工作专注于开发和评估单剂量缓释乙型肝炎表面抗原 (HBsAg) 负载纳米疫苗用于乙型肝炎。传统治疗方法存在重复给药的问题，因此需要加强剂量。因此，我们利用中心复合设计，通过双乳液溶剂蒸发技术开发了 HBsAg 的聚合物纳米疫苗，用于制剂优化。还研究了独立变量（如聚合物用量、稳定剂浓度、水/有机相比例和匀浆速度）对关键质量属性（如粒径和包封效率）的影响。纳米疫苗的理化性质、释放、内化以及通过不同途径（如口服、皮下、鼻内和肌肉内）给药后在 BALB/c 小鼠体内的免疫评价等方面进行了表征。设计的纳米疫苗表现出纳米级尺寸、光滑表面、负 zeta 电位、最大包封率、缓释和更好的巨噬细胞和 MRC-5 细胞系内化。通过测量抗 HBsAg 滴度（如特异性免疫球蛋白 IgG 和 IgA 反应）和细胞因子水平（白细胞介素 2、干扰素-Y）测量，评估了不同途径给药的纳米疫苗的免疫刺激活性。结果表明，肌肉内途径给药的纳米疫苗产生了更好的体液和细胞反应，并且作为单剂量通过肌肉内途径给药的抗原传递的潜在载体。
