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Hybrid liposomes coated with amphiphilic hyaluronic acid derivative for targeted anticancer drug delivery and imaging
표적화된 항암제 전달 및 이미징을 위한 양친매성 히알루론산 유도체를 코팅한 하이브리드형 리포좀

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Authors
박주환
Advisor
김대덕
Major
약학대학 약학과
Issue Date
2016-02
Publisher
서울대학교 대학원
Keywords
HACEnanoliposomal formulationtumor targetingdrug deliveryMR imagingpharmacokinetic property
Description
학위논문 (박사)-- 서울대학교 대학원 : 약학대학 약학과 약제과학전공, 2016. 2. 김대덕.
Abstract
Nanohybrid liposomes coated with amphiphilic hyaluronic acid–ceramide (HACE) was developed for targeted delivery of anticancer drug and in vivo cancer imaging. Doxorubicin (DOX) and Magnevist were used as a model anticancer drug and a magnetic resonance (MR) imaging probe, respectively. Nano-sized liposomal formulation which has mean diameter ranged from 120 to 130 nm and a narrow size distribution was developed. Encapsulation efficiency of DOX in liposomes was higher than 50%, and zeta potential of HACE-used liposomes (F3) was negatively higher than that of control liposomes (F2), indicating that liposomal surface was coated with HACE. When the particle size distribution of both formulations was monitored in serum condition, HACE-coated liposomes showed enhanced stability than control liposomes, without forming aggregation. The prepared formulation showed sustained release profile and the release rate of DOX was increased in acidic pH than in physiological pH. In vitro cytotoxicity study, HACE-coated liposomes exhibited reduced cytotoxicity compared with control liposomes. In cellular uptake study, uptake of DOX from HACE-coated liposomes was improved by the interaction between HA and CD44 receptor. By MR imaging study, HACE-coated liposomes were demonstrated to have enhanced diagnostic activity with passive targeting and active targeting. In a pharmacokinetic study in rats, DOX encapsulated in liposomal formulation showed significantly prolonged circulation compared to DOX solution. In addition, pharmacokinetic parameters of liposomal formulation were further enhanced by surface coating with HACE, indicating that introducing HACE can increase in vivo stability. Based on these results, the HACE-coated nanoliposomal formulation may be a promising delivery system for targeted cancer therapy and cancer diagnosis.
Language
English
URI
https://hdl.handle.net/10371/120126
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Theses (Ph.D. / Sc.D._약학과)
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