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Reduction-Sensitive Reversibly Crosslinked Biodegradable Micelles for Triggered Release of Doxorubicin
作者:Y.M. Xu, F.H. Meng*, R. Cheng, Z.Y. Zhong*
關鍵字:Reduction-sensitive, drug delivery, micelle
論文來源:期刊
具體來源:Macromol. Biosci.
發表時間:2009年

Reduction-responsive reversibly crosslinked biodegradable micelles were developed and applied for triggered release of doxorubicin (DOX). An amphiphilic block copolymer of poly(ethylene glycol) (PEG) and poly(e-caprolactone) (PCL) that contains two lipoyl functional groups at their interface (PEG-L2-PCL) has been synthesized. 1H NMR spectroscopy and gel permeation chromatography
(GPC) measurements show that the PEG-L2-PCL block copolymer had a controlled composition (PEG 5 kDa and PCL 5.4 kDa) and a polydispersity index (PDI) of 1.36. PEG-L2-PCL formed micelles with sizes that ranged from 20 to 150nm in aqueous solutions, wherein a critical micelle concentration (CMC) of 16mgL1 was determined. The micelles were readily crosslinked by adding 7.6 mol % of dithiothreitol (DTT) relative to the lipoyl groups. Notably, micelles after crosslinking demonstrated a markedly enhanced stability against dilution, physiological salt concentration, and organic solvent. In the presence of 10103 M DTT, however, micelles were subject to rapid de-crosslinking. In vitro release studies showed minimal release of DOX from crosslinked micelles at a concentration of 10mgL1 (C<CMC, analogous to intravenous injection), wherein less than 15% of the DOX was released in 10 h. In contrast, rapid release of DOX was observed for DOX-loaded non-crosslinked micelles under otherwise the same conditions (80% release in 0.5 h). In the presence of 10103 M DTT mimicking an intracellular reductive environment, sustained release of DOX from crosslinked micelles
was achieved, in which 75% of the DOX was released in 9 h. These novel reduction-sensitive reversibly crosslinked biodegradable micelles are highly promising for targeted intracellular delivery of anticancer drugs.

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