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Preparation and characterization of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel : 도세탁셀의 약물전달을 위한 저분자량 헤파린과 스테아릴아민 중합체를 이용한 자가조립나노입자의 제조 및 평가
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- Authors
- Advisor
- 김대덕
- Major
- 약학대학 약학과
- Issue Date
- 2015-02
- Publisher
- 서울대학교 대학원
- Description
- 학위논문 (박사)-- 서울대학교 대학원 : 약학과, 2015. 2. 김대덕.
- Abstract
- Part Ⅱ. Characterization and evaluation of self-assembled nanoparticles based on low-molecular-weight heparin and stearylamine conjugates for controlled delivery of docetaxel
Low-molecular-weight heparin (LMWH)–stearylamine (SA) conjugates (LHSA)-based self-assembled nanoparticles were prepared for intravenous delivery of docetaxel (DCT). 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide were used as coupling agents for synthesis of LHSA conjugates. The physicochemical properties, in vitro antitumor efficacy, in vitro cellular uptake efficiency, in vivo antitumor efficacy, and in vivo pharmacokinetics of LHSA nanoparticles were investigated. The LHSA nanoparticles exhibited a spherical shape with a mean diameter of 140–180 nm and a negative surface charge. According to in vitro release and in vivo pharmacokinetic test results, the DCT-loaded LHSA5 (LMWH:SA = 1:5) nanoparticles exhibited sustained drug release profiles. The blank LHSA nanoparticles demonstrated only an insignificant cytotoxicity in MCF-7 and MDAMB 231 human breast cancer cells
additionally, higher cellular uptake of coumarin 6 (C6) in MCF-7 and MDAMB 231cells was observed in the LHSA5 nanoparticles group than that in the C6 solution group. The in vivo tumor growth inhibition efficacy of DCT-loaded LHSA5 nanoparticles was also significantly higher than the Taxotere-treated group in the MDAMB 231 tumor xenografted mouse model. These results indicated that the LHSA5-based nanoparticles could to be a promising anticancer drug delivery system.
- Language
- English
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