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Evaluation of the Physicochemical Properties, Pharmacokinetics, and In Vitro Anticancer Effects of Docetaxel and Osthol Encapsulated in Methoxy Poly(ethylene glycol)-b-Poly(caprolactone) Polymeric Micelles

Authors
Jo, Min JeongLee, Yu JinPark, Chun-WoongChung, Youn BokKim, Jin-SeokLee, Mi KyeongShin, Dae Hwan
Issue Date
Jan-2021
Publisher
MDPI
Keywords
docetaxel; osthol; mPEG-b-PCL polymeric micelles; combination therapy; pharmacokinetics
Citation
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.22, no.1, pp.1 - 16
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume
22
Number
1
Start Page
1
End Page
16
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/146842
DOI
10.3390/ijms22010231
ISSN
1661-6596
Abstract
Docetaxel (DTX), a taxane-based anticancer drug, and osthol (OTH), a coumarin-derivative compound, have shown anticancer effects against different types of cancers through various mechanisms. However, these drugs have low solubility in water and low oral bioavailability, and thus their clinical application is difficult. To overcome these problems, we encapsulated DTX and OTH in methoxy poly(ethylene glycol)-b-poly(caprolactone) (mPEG-b-PCL) and conducted studies in vitro and in vivo. We selected a 1:4 ratio as the optimal ratio of DTX and OTH, through combination index analysis in A549 cancer cells, and prepared micelles to evaluate the encapsulation efficiency, drug loading, particle size, and zeta potential. The in vitro drug-release profile showed that DTX/OTH-loaded mPEG-b-PCL micelles could slowly release DTX and OTH. In the clonogenic assay, DTX/OTH-loaded mPEG-b-PCL micelles showed 3.7 times higher inhibitory effect than the DTX/OTH solution. Pharmacokinetic studies demonstrated that micelles in combination with DTX and OTH exhibited increased area under curve and decreased clearance values, as compared with single micelles.
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