万古霉素缓释微球的制备及其质量评价

doi:10.3760/cma.j.issn.1007-1245.2024.14.026

国际医药卫生导报 ›› 2024, Vol. 30 ›› Issue (14): 2413-2418.DOI: 10.3760/cma.j.issn.1007-1245.2024.14.026

万古霉素缓释微球的制备及其质量评价

宋远征¹ 叶演² 巩守超³ 张玉东⁴ 刘志¹ 孙红武² 曾浩²

¹徐州医科大学附属滕州市中心人民医院骨创外科，滕州　277599；²陆军军医大学药学与检验医学系微生物与生化药学教研室，重庆　400038；³徐州医科大学附属滕州市中心人民医院整形美容科，滕州　277599；⁴徐州医科大学第一临床学院，徐州　221004

收稿日期:2024-04-01 出版日期:2024-07-15 发布日期:2024-08-05
通讯作者: 巩守超，Email：tzzxrmyy20130101@163.com
基金资助:
国家自然科学基金（32070924）；徐州医科大学附属医院科技发展计划（XYFY2020020）

Preparation and quality evaluation of sustained-release microspheres loaded with vancomycin

Song Yuanzheng¹, Ye Yan², Gong Shouchao³, Zhang Yudong⁴, Liu Zhi¹, Sun Hongwu², Zeng Hao²

¹Department of Orthopaedic Surgery, Tengzhou Central People's Hospital Affiliated to Xuzhou Medical University, Tengzhou 277599, China; ²Department of Microbiology and Biochemical Pharmacy, Army Medical University, Chongqing 400038, China; ³Department of Plastic Surgery and Cosmetology, Tengzhou Central People's Hospital Affiliated to Xuzhou Medical University, Tengzhou 277599, China; ⁴The First Clinical College, Xuzhou Medical University, Xuzhou 221004, China

Received:2024-04-01 Online:2024-07-15 Published:2024-08-05
Contact: Gong Shouchao, Email: tzzxrmyy20130101@163.com
Supported by:
National Natural Science Foundation of China (32070924); Science and Technology Development Plan of Xuzhou Medical University Affiliated Hospital (XYFY2020020)

摘要/Abstract

摘要：

目的　制备质量稳定、安全有效的载万古霉素缓释微球，评价其质量特征。方法　采用复乳溶剂挥发法将聚乳酸（polylactic acid，PLA）和聚乳酸-羟基乙酸共聚物［poly（lactic-co-glycolic acid），PLGA］按3种不同比例混合制备万古霉素微球进行筛选；利用单因素实验，研究不同浓度聚乙烯醇（polyvinyl alcohol，PVA）、内外水相比例对微球粒径、包封率、载药量的影响后并制备出优选的载万古霉素的PLA/PLGA缓释微球；对其体内外抗多重耐药菌耐甲氧西林金黄色葡萄球菌（methicillin-resistant Staphylococcus aureus，MRSA）进行药效学研究。采用单因素方差分析。结果　内外水相比和PVA浓度对万古霉素的包封率和载药量影响不大（P>0.05），但微球中PLA和PLGA质量比对万古霉素的包封率和载药量差异有统计学意义（P<0.000 1），纯PLA时微球平均粒径［（41.95 µm）］、包封率［（28.87±0.32）%］和载药量［（17.80±0.21）%］最大。万古霉素微球对MRSA 252的抗菌活性高于其水溶液（最小抑菌浓度0.391 ng/L比0.781 ng/L）（P<0.000 1）。万古霉素微球治疗受损皮肤感染MRSA 252比相同浓度的万古霉素水溶液具有更满意的杀菌活性（P<0.05）。万古霉素微球对感染MRSA 252小鼠的伤口治愈效果比万古霉素水溶液更好。结论　通过优选获得的微球处方，制备的PLA/PLGA缓释微球可实现万古霉素药物的局部可控释放，通过调节PLA和PLGA在共混物中的比例提高药物包封率和载药量、定制降解速率、改变药物释放，是有效对抗金黄色葡萄球菌感染的制剂。

关键词:

聚乳酸, 聚乳酸-羟基乙酸共聚物, 万古霉素, 缓释微球, 耐甲氧西林金黄色葡萄球菌

Abstract:

Objective　To prepare stable, safe, and effective vancomycin sustained-release microspheres and evaluate their quality characteristics. Methods　Vancomycin microspheres were prepared by mixing polylactic acid (PLA) and poly (lactic-co-glycolic acid) (PLGA) in three different proportions by solvent volatilization method. The effects of different concentrations of polyvinyl alcohol (PVA), the ratio of internal water phase to external water phase on size, encapsulation rate, and drug loading of the microspheres were studied by single factor experiment, and the optimal PLA/PLGA sustained-release microspheres loaded with vancomycin were prepared. The pharmacodynamics of methicillin-resistant Staphylococcus aureus (MRSA) were studied in vivo and in vitro. One-way analysis of variance was used. Results　The concentration of PVA and ratio of internal water phase to external water phase had little effect on the encapsulation rate and drug loading of vancomycin (P>0.05), but the mass ratio of PLA and PLGA in microspheres had significant effects on the encapsulation rate and drug loading of vancomycin (P<0.000 1). The microsphere size (41.95 μm), encapsulation rate [(28.87±0.32)%], and drug loading [(17.80±0.21)%] were the largest when PLA was pure. The antibacterial activity of vancomycin microspheres against MRSA 252 was higher than that of aqueous solution (0.391 ng/L vs. 0.781 ng/L) (P<0.000 1). Vancomycin microspheres showed more satisfactory bactericidal activity in the treatment of MRSA 252 than vancomycin aqueous solution with the same concentration (P<0.05). The wound healing effect of vancomycin microspheres on MRSA 252 infected mice was better than that of vancomycin aqueous solution. Conclusions　The prepared PLA/PLGA sustained release microspheres can achieve local controlled release of vancomycin drug by adjusting the proportion of PLA and PLGA in the blend to improve drug encapsulation rate and drug loading, tailor degradation rate and change drug release, which is an effective preparation against Staphylococcus aureus infection.

Key words:

Polylactic acid, Poly (lactic-co-glycolic acid), Vancomycin, Sustained release microspheres, MRSA

宋远征叶演巩守超张玉东刘志孙红武曾浩.

万古霉素缓释微球的制备及其质量评价 [J]. 国际医药卫生导报, 2024, 30(14): 2413-2418.

Song Yuanzheng, Ye Yan, Gong Shouchao, Zhang Yudong, Liu Zhi, Sun Hongwu, Zeng Hao.

Preparation and quality evaluation of sustained-release microspheres loaded with vancomycin [J]. International Medicine and Health Guidance News, 2024, 30(14): 2413-2418.

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万古霉素缓释微球的制备及其质量评价

Preparation and quality evaluation of sustained-release microspheres loaded with vancomycin

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