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  • Title: Deoxycholic acid-modified chitooligosaccharide/mPEG-PDLLA mixed micelles loaded with paclitaxel for enhanced antitumor efficacy.
    Author: Jiang C, Wang H, Zhang X, Sun Z, Wang F, Cheng J, Xie H, Yu B, Zhou L.
    Journal: Int J Pharm; 2014 Nov 20; 475(1-2):60-8. PubMed ID: 25152167.
    Abstract:
    Poly(ethylene glycol) (PEG) as a block in polymeric micelles can prolong circulation life and reduce systemic clearance but decrease the cellular uptake. To overcome this limitation, a mixed micelle composed of deoxycholic acid-modified chitooligosaccharide (COS-DOCA) and methoxy poly(ethylene glycol)-polylactide copolymer (mPEG-PDLLA) was designed to load paclitaxel (PTX). The PTX-loaded mixed micelles was prepared by nanoprecipitation method with high drug-loading efficiency of 8.03% and encapsulation efficiency of 97.09% as well as small size (∼40 nm) and narrow size distribution. COS-DOCA/mPEG-PDLLA mixed micelles exhibited the sustained release property. Due to the positive charge and bioadhesive property of COS-DOCA, the cellular uptake of PTX in mixed micelles was higher in cancer cells but lower in macrophage cells compared to the mPEG-PDLLA micelles. The systemic toxicity of PTX in mixed micelles was much lower than Taxol using zebrafish as a toxicological model. Furthermore, the PTX-loaded COS-DOCA/mPEG-PDLLA mixed micelles can prolong the blood circulation time of PTX and enhance the antitumor efficacy in A549 lung xenograft model. Our findings indicate that COS-DOCA/mPEG-PDLLA mixed micelles could be a potential vehicle for enhanced delivery of anticancer drugs.
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