恩替卡韦负载的聚（乳酸 - 共 - 羟基乙酸）微球用于长期治

StephenW

Int J Pharm. 2019 Jan 31. pii: S0378-5173(19)30093-6. doi: 10.1016/j.ijpharm.2019.01.052. [Epub ahead of print]
Entecavir-loaded poly (lactic-co-glycolic acid) microspheres for long-term therapy of chronic hepatitis-B: preparation and in vitro and in vivo evaluation.
Zhang C1, Wang A2, Wang H3, Yan M3, Liang R2, He X4, Fu F2, Mu H4, Sun K5.
Author information

1
    School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, Shandong Province, People's Republic of China; School of Pharmacy, Jining Medical University, Jining, Shandong Province, People's Republic of China.
2
    School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, Shandong Province, People's Republic of China; State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd, Yantai, Shandong Province, People's Republic of China.
3
    School of Pharmacy, Jining Medical University, Jining, Shandong Province, People's Republic of China.
4
    School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, Shandong Province, People's Republic of China.
5
    School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, Shandong Province, People's Republic of China. Electronic address: [email protected].

Abstract

To avoid severe exacerbations in the load of hepatitis B virus (HBV) as a consequence of discontinuous use of anti-HBV drugs, entecavir (ETV), the first-line anti-HBV drug, was primally formulated as extended-release poly (lactic-co-glycolic acid) microspheres in the present study. Because ETV is slightly soluble in water and in some other organic solvents used for microsphere preparation, methods for solid-microencapsulation were employed to fabricate the ETV microspheres. The optimized microspheres were evaluated for their morphology, particle size, drug loading, in vitro drug release, and in vivo pharmacokinetics in rats. The optimized formulation was found to have a mean particle size of 86 µm and drug loading of 13%. Differential scanning calorimetry and powder X-ray diffraction indicated that ETV existed in crystal, amorphous, and molecular states in the microspheres. In vitro and in vivo release revealed that the dissolution of ETV dominated the release process. The morphology of the microspheres and changes in the morphology during in vitro release were assessed by scanning electron microscopy. The novel ETV-MS described in this study should have great potential for clinical use as an alternative treatment against HBV.

Copyright © 2019. Published by Elsevier B.V.
KEYWORDS:

Biodegradable microsphere; Chronic hepatitis-B; Entecavir; Extended release; PLGA

PMID:
    30711615
DOI:
    10.1016/j.ijpharm.2019.01.052

StephenW

Int J Pharm。 2019年1月31日.pii：S0378-5173（19）30093-6。 doi：10.1016 / j.ijpharm.2019.01.052。 [印刷前的电子版]
恩替卡韦负载的聚（乳酸 - 共 - 羟基乙酸）微球用于长期治疗慢性乙型肝炎：制剂和体外和体内评估。
Zhang C1，Wang A2，Wang H3，Yan M3，Liang R2，He X4，Fu F2，Mu H4，Sun K5。
作者信息

1
    山东省烟台大学药学院，山东省高校药物传递系统与生物技术药物协同创新中心，烟台大学分子药理学与药物评价重点实验室，烟台大学，中华人民共和国;中华人民共和国济宁医学院药学院，山东省济宁市。
2
    山东省烟台大学药学院，山东省高校药物传递系统与生物技术药物协同创新中心，烟台大学分子药理学与药物评价重点实验室，烟台大学，中华人民共和国;中华人民共和国山东省烟台市山野鹿野药业有限公司长效靶向给药系统国家重点实验室。
3
    中华人民共和国济宁医学院药学院，山东省济宁市。
4
    山东省烟台大学药学院，先进药物输送系统与生物技术药物协同创新中心，烟台大学分子药理学与药物评价重点实验室，烟台大学，中华人民共和国山东省烟台市。
五
    山东省烟台大学药学院，先进药物输送系统与生物技术药物协同创新中心，烟台大学分子药理学与药物评价重点实验室，烟台大学，中华人民共和国山东省烟台市。电子地址：[email protected]。

抽象

为了避免由于不连续使用抗HBV药物引起乙型肝炎病毒（HBV）严重恶化，一线抗乙肝病毒药物恩替卡韦（ETV）最初配制为缓释聚乙烯（乳酸）在本研究中，-co-乙醇酸）微球。由于ETV微溶于水和用于微球制备的一些其它有机溶剂，因此采用固 - 微胶囊化方法制备ETV微球。评估优化的微球的形态，粒度，载药量，体外药物释放和大鼠体内药代动力学。发现优化的制剂具有86μm的平均粒度和13％的载药量。差示扫描量热法和粉末X射线衍射表明ETV存在于微球中的晶体，无定形和分子状态。体外和体内释放显示ETV的溶解主导释放过程。通过扫描电子显微镜评估微球的形态和体外释放期间的形态变化。本研究中描述的新型ETV-MS应具有很大的临床应用潜力，可作为抗HBV的替代疗法。

版权所有©2019。Elsevier B.V.
关键词：

可生物降解的微球;慢性乙型肝炎;恩替卡韦;缓释; PLGA

结论：
    30711615
DOI：
    10.1016 / j.ijpharm.2019.01.052