Abstract:
:The inferior in vivo stability of micellar drugs has been a prime challenge for their application in targeted drug delivery. Here we report on novel galactose-decorated covalently cross-linked biodegradable micelles based on photo-cross-linkable poly(ethylene glycol)-b-poly(acryloyl carbonate)-b-poly(ε-caprolactone) (PEG-PAC-PCL) and galactose-conjugated PEG-PCL (Gal-PEG-PCL) copolymers for enhanced hepatoma-targeting delivery of paclitaxel (PTX). The molecular weight of PEG in Gal-PEG-PCL was higher than that in PEG-PAC-PCL, thereby fully exposing Gal ligands at the micellar surface. These micelles, either with or without loading of PTX, were readily cross-linked by UV irradiation to afford micelles with small sizes (ca. 79-94 nm) and enhanced stability. The in vitro release studies confirmed that drug release from cross-linked micelles was significantly inhibited. Interestingly, MTT assays showed that Gal-decorated PTX-loaded cross-linked micelles retained a high antitumor activity in HepG2 cells, which was much more effective than PTX-loaded cross-linked micelles without Gal ligands and comparable to Gal-decorated PTX-loaded non-cross-linked micelles. Remarkably, the preliminary in vivo antitumor efficacy studies in SMMC-7721 tumor (human hepatoma)-bearing nude mice revealed that Gal-decorated PTX-loaded cross-linked micelles inhibited the growth of the human hepatoma more effectively than PTX-loaded cross-linked micelles as well as Gal-decorated PTX-loaded non-cross-linked micelles. These results indicate that Gal-decorated cross-linked PEG-PCL micelles have great potential in liver tumor-targeted chemotherapy.
journal_name
Biomacromoleculesjournal_title
Biomacromoleculesauthors
Yang R,Meng F,Ma S,Huang F,Liu H,Zhong Zdoi
10.1021/bm2006856subject
Has Abstractpub_date
2011-08-08 00:00:00pages
3047-55issue
8eissn
1525-7797issn
1526-4602journal_volume
12pub_type
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