Stabilization and immune response of HBsAg encapsulated within poly (lactic-co-glycolic acid) microspheres using HSA as a stabilizer
Stabilization and immune response of HBsAg encapsulated within poly (lactic-co-glycolic acid) microspheres using HSA as a stabilizer
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DOI：
10.1016/j.ijpharm.2015.10.004
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发表时间：
2015-12-30
影响因子：
5.8
通讯作者：
Wang, Gaizhen
中科院分区：
文献类型：
--
作者：
Xu, Wenjuan;He, Jintian;Wang, Gaizhen
以人血清白蛋白（HSA）为稳定剂，制备载B型肝炎病毒表面抗原（HBsAg）的聚乳酸-羟基乙酸共聚物（PLGA）微球。用二氯甲烷冷冻干燥和乳化乙型肝炎表面抗原溶液会导致乙型肝炎表面抗原抗原性的相当大的损失。因此，研究了HSA和海藻糖对冻干和乳化过程中HBsAg回收率的影响。在冻干和乳化过程中，向HBsAg溶液中加入HSA显著提高了抗原回收率至>90%。考察了共包封HSA对PLGA微球的性质及释放HBsAg稳定性的影响。体外释放试验表明，HBsAg可从PLGA微球中持续释放70 d以上。大量释放的HBsAg在没有HSA共包封的情况下是无活性的。相反，在HSA共包封的情况下，释放的HBsAg保留了约90%的抗原性。大鼠单次注射载HBsAg-HSA的PLGA微球导致抗HBsAg IgG和Th 1细胞因子水平高于单次注射载HBsAg的微球或两次注射常规铝佐剂HBsAg疫苗。基于这些发现，载HBsAg-HSA的PLGA微球可能是HBsAg的有效载体，并形成有希望的贮库系统。(C)2015 Elsevier B. V.版权所有。
The aim of this study was to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres containing hepatitis B virus surface antigen (HBsAg) using human serum albumin (HSA) as a stabilizer. Lyophilization and emulsification of HBsAg solution with dichloromethane caused a considerable loss of HBsAg antigenicity. Thus, the effects of HSA and trehalose on HBsAg recovery during lyophilization and emulsification were investigated. Adding HSA to HBsAg solutions significantly improved antigen recovery to >90% during lyophilization and emulsification. The effects of co-encapsulated HSA on the characteristics of the PLGA microspheres and stability of HBsAg released from the microspheres were also investigated. The in vitro release test showed that HBsAg was released from the PLGA microspheres continuously over seventy days. A large amount of released HBsAg was inactive without co-encapsulation of HSA. On the contrary, with HSA co-encapsulation, the released HBsAg retained approximately 90% of its antigenicity. The single injection of the HBsAg-HSA-loaded PLGA microspheres in rats resulted in higher anti-HBsAg IgG and Th1 cytokine levels than the single injection of the HBsAg-loaded microspheres or two injections of the conventional aluminum-adjuvanted HBsAg vaccine. Based on these findings, the HBsAg-HSA-loaded PLGA microspheres could be an effective carrier for HBsAg and form a promising depot system. (C) 2015 Elsevier B.V. All rights reserved.