表面官能化，pH响应聚（乳酸 - 共 - 乙醇酸）鼻内疫苗递送的

StephenW

Eur J Pharm Biopharm. 2016 Aug 25. pii: S0939-6411(16)30465-9. doi: 10.1016/j.ejpb.2016.08.012. [Epub ahead of print]
Surface-functionalized, pH-responsive poly(lactic-co-glycolic acid)-based microparticles for intranasal vaccine delivery: effect of surface modification with chitosan and mannan.Li Z1, Xiong F1, He J2, Dai X1, Wang G3.
Author information

• 1College of Life Science, Hebei Normal University, NO.20 Road East of 2nd Ring South, Shijiazhuang City, Hebei Province 050024, People's Republic of China.
• 2College of Life Science, Hebei Normal University, NO.20 Road East of 2nd Ring South, Shijiazhuang City, Hebei Province 050024, People's Republic of China. Electronic address: [email protected].
• 3College of Environmental Science and Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, China. Electronic address: [email protected].
  

AbstractIn the present study, surface-functionalized, pH-responsive poly(lactic-co-glycolic acid) (PLGA) microparticles were investigated for nasal delivery of hepatitis B surface Antigen (HBsAg). pH-responsive PLGA, chitosan modified PLGA (CS-PLGA), mannan modified PLGA (MN-PLGA), mannan and chitosan co-modified PLGA (MN-CS-PLGA) microparticles were prepared utilizing a double-emulsion method. Antigen released rapidly from four types of microparticles at pH5.0 and pH 6.0, but slowly released at pH 7.4. Mannan and chitosan surface modification enhanced intracellular microparticle uptake by macrophages. Following intracellular macrophage antigen uptake, antigen release occurred in three different patterns: fast release from PLGA and MN-PLGA microparticles in endosomes/lysosomes, slow release from CS-PLGA microparticles in cytoplasm and a combination of fast release and slow release patterns from MN-CS-PLGA microparticles. Furthermore, chitosan coating modification increased the residence time of CS-PLGA and MN-CS-PLGA microparticles in the nasal cavity. In vivo immunogenicity studies indicated that MN-CS-PLGA microparticles induced stronger humoral and cell-mediated immune responses compared with PLGA, MN-PLGA and CS-PLGA microparticles. These results suggest that surface modification of pH-responsive PLGA microparticles with mannan and chitosan is a promising tool for nasal delivery of HBsAg.
Copyright © 2016. Published by Elsevier B.V.


KEYWORDS: Antigen intracellular release; Chitosan; Intranasal vaccination; Mannan; PLGA microparticles; pH-responsive

PMID:27569030DOI:10.1016/j.ejpb.2016.08.012

StephenW

欧元J医药生物制药。 2016年25月PII：S0939-6411（16）30465-9。 DOI：10.1016 / j.ejpb.2016.08.012。 [打印EPUB提前]
表面官能化，pH响应聚（乳酸 - 共 - 乙醇酸）鼻内疫苗递送的基于微粒：用壳聚糖和甘露聚糖的表面改性的效果。
李Z1，熊F1，他J2，戴X1，G3王。
作者信息

    生命科学，河北师范大学，二环南，石家庄市的20号路东学院，河北050024，中​​国的人民共和国。
    生命科学，河北师范大学，二环南，石家庄市的20号路东2College，河北050024，中​​国的人民共和国。电子地址：[email protected]。
    环境科学与工程，科学与技术，石家庄050018，中国的河北工业大学3College。电子地址：[email protected]。

抽象

在本研究中，表面官能化，pH响应聚（乳酸 - 共 - 乙醇酸）（PLGA）微粒进行了研究乙型肝炎表面抗原（HBsAg）的经鼻递送。 pH响应PLGA，脱乙酰壳多糖改性的PLGA（CS-PLGA），甘露聚糖改性的PLGA（MN-PLGA），甘露聚糖和脱乙酰壳多糖共改性的PLGA（MN-CS-PLGA）微粒制备利用双乳液法。抗原从四种类型的微粒的在pH5.0和pH6.0的快速释放，但是在pH7.4缓慢释放。甘露聚糖和壳聚糖表面改性被巨噬细胞内增强吸收微粒。以下细胞巨噬细胞抗原摄取，抗原释放发生在三个不同的模式：从内涵体/溶酶体PLGA和MN-PLGA微粒，从CS-PLGA微粒在细胞质缓慢释放和快速释放并从MN-缓慢释放模式的组合快速释放CS-PLGA微粒。此外，脱乙酰壳多糖包衣修饰在鼻腔中增加的CS-PLGA和MN-CS-PLGA微粒的停留时间。体内的免疫原性研究表明，MN-CS-PLGA微粒与PLGA，MN-PLGA和CS-PLGA微粒相比诱导更强的体液和细胞介导的​​免疫反应。这些结果表明，pH响应的PLGA微粒与甘露聚糖和脱乙酰壳多糖的表面改性为乙肝表面抗原的经鼻递送的有前景的工具。

版权所有©2016年出版由Elsevier B.V.
关键词：

抗原细胞内释放;壳聚糖;鼻内接种;甘露; PLGA微粒; pH响应

结论：
    27569030
DOI：
    10.1016 / j.ejpb.2016.08.012