用于阴道黏膜给药的纳米胶束复合温敏水凝胶的制备及性能评价

doi:10.11896/cldb.22040117

材料导报

2023, Vol. 37

Issue (19): 22040117-7 https://doi.org/10.11896/cldb.22040117

高分子与聚合物基复合材料

用于阴道黏膜给药的纳米胶束复合温敏水凝胶的制备及性能评价

何贤会¹, 杨培昕¹, 卢小鸾¹, 汤陆扬¹, 付阳洋¹, 彭黔荣^2,*, 杨敏^1,*

1 贵州大学药学院,贵阳 550025
2 中国烟草贵州中烟工业有限责任公司,贵阳 550025

Preparation and Evaluation of Nano Micelles Composite Thermosensitive Hydrogels for Vaginal Mucosa Administration

HE Xianhui¹, YANG Peixin¹, LU Xiaoluan¹, TANG Luyang¹, FU Yangyang¹, PENG Qianrong^2,*, YANG Min^1,*

1 School of Pharmacy, Guizhou University, Guiyang 550025, China
2 China Tobacco Guizhou Industrial Co., Ltd., China Tobacco, Guiyang 550025, China

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摘要宫颈癌的发生与人乳头瘤病毒(HPV)感染密切相关。治疗HPV感染可有效预防宫颈癌。洛匹那韦(LPV)是Food and Drug Administration(FDA)批准的抗艾滋病病毒的治疗药物,研究发现洛匹那韦具有抗HPV病毒的活性。本工作旨在制备一种负载LPV的纳米胶束复合水凝胶载药系统,探究其通过阴道黏膜局部给药的性能。采用两亲性聚合物维生素E聚乙二醇琥珀酸酯(TPGS)和助渗透剂牛磺脱氧胆酸钠(STDC)自组装制备混合载药胶束(TPGS-STDC/LPV),混合胶束分散在温敏凝胶中形成载药纳米胶束复合温敏水凝胶(NMCH)。对TPGS-STDC/LPV的粒径、ZETA电位、形貌、包封率、载药量和释药等进行了检测,还测试了NMCH的黏膜粘附性、药物释放、透皮渗透和抗病毒活性等。实验结果表明,TPGS-STDC/LPV具有高药物包封率、高载药量,累积释放率达(96.82±2.93)%(pH=4.5,72 h),表现出酸响应释放性能;复合水凝胶具有适宜人体的温敏特性,对阴道上皮黏膜具有优异的粘附性,所制备的NMCH的LPV渗透率最好,为(54.05±2.74)%,约为游离LPV的7.4倍;NMCH具有显著的抗HPV病毒活性。该体系适合用于阴道局部给药。

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	何贤会
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	付阳洋
	彭黔荣
	杨敏

关键词: HPV病毒洛匹那韦纳米混合胶束纳米胶束复合温敏水凝胶阴道局部给药

Abstract: The occurrence of cervical cancer is closely related to infection with human papillomavirus (HPV). Treatment of HPV infection is effective for preventing the development of cervical cancer. Lopinavir (LPV) is an anti-HIV drug approved by FDA, and it was found that LPV has anti-HPV activity. The aim of this study was to develop a nano-micelles composite hydrogel drug delivery system loaded LPV and explore its perfor-mance for local administration through vaginal mucosa. LPV-loaded mixed micelles (TPGS-STDC/LPV) were prepared by the self-assembly of amphiphilic polymer TPGS, penetrant STDC, and LPV, then were dispersed into the thermosensitive hydrogel to form LPV-loaded nano-micelles composite hydrogel (NMCH). The particle size, zeta potential, morphology, entrapment efficiency, drug loading and drug release of TPGS-STDC/LPV were detected. The mucosal adhesion, drug release, transdermal penetration and antiviral activity of NMCH were also tested. The results showed that TPGS-STDC/LPV exhibited high entrapment efficiency and high drug loading, and the cumulative release of LPV achieved (96.82±2.93)% with pH of 4.5 at 72 h, Showing a good acid-response drug release. NMCH had a human temperature sensitive nature and good adhesion to the vaginal epithelial mucosa, and the skin permeation rate of LPV (54.05±2.74)% was observed about 7.4 times that of free LPV, and NMCH displayed good anti-HPV activities. This drug delivery system could be suitable for topical vaginal administration.

Key words: HPV virus lopinavir nano-mixed micelles nano micelles composite thermosensitive hydrogel vaginal topical administration

出版日期: 2023-10-10 发布日期: 2023-09-28

ZTFLH:

O636

基金资助: 国家自然科学基金(21562014);贵州中烟工业有限公司项目(GZZY/KJ/JS/2014_Y005-1)

通讯作者: *杨敏,贵州大学药学院教授、硕士研究生导师,1983年贵州工学院有机化工专业本科毕业,1998年四川联合大学应用化学专业在职研究生进修班结业,2006年四川大学有机化学专业博士毕业。1983年到1999年在贵州省轻工科研所工作,1999年到贵州大学贵州至今。目前主要从事药物制剂、纳米催化和药物递送,生物材料等方面的教学与科研工作。发表论文98篇,包括Journal of Polymer Research、Tetrahedron Letters、Chemical Physics Letters、Current Pharmaceutical Analysis等。 3435391@qq.com; 彭黔荣,贵州中烟技术中心研究员,贵州大学化学与化工学院硕士生导师,1983年贵州工学院有机化工专业本科毕业,1998年四川联合大学化学工程专业硕士毕业,2004年四川大学化学工程专业博士毕业。1983年到2004年在贵州大学化工学院工作,2004年到贵州中烟工作至今。目前主要从事烟草化学、近红外光谱技术应用和凝胶化学与应用等方面的科研工作。发表论文110余篇,授权专利20项,包括Journal of Polymer Research、Tetrahedron Letters、 Chemical Physics Letters、Current Pharmaceutical Analysis、《烟草化学》等。2578973180@qq.com

作者简介: 何贤会,贵州大学在读研究生。2019年9月贵州大学获得理学学士学位,在杨敏、彭黔荣教授的指导下进行研究。目前主要从事疏水药物纳米递送系统的研究。

引用本文:

何贤会, 杨培昕, 卢小鸾, 汤陆扬, 付阳洋, 彭黔荣, 杨敏. 用于阴道黏膜给药的纳米胶束复合温敏水凝胶的制备及性能评价[J]. 材料导报, 2023, 37(19): 22040117-7.
HE Xianhui, YANG Peixin, LU Xiaoluan, TANG Luyang, FU Yangyang, PENG Qianrong, YANG Min. Preparation and Evaluation of Nano Micelles Composite Thermosensitive Hydrogels for Vaginal Mucosa Administration. Materials Reports, 2023, 37(19): 22040117-7.

链接本文:

http://www.mater-rep.com/CN/10.11896/cldb.22040117 或 http://www.mater-rep.com/CN/Y2023/V37/I19/22040117

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