alexa Reduction-sensitive reversibly crosslinked biodegradable micelles for triggered release of doxorubicin.
Materials Science

Materials Science

Journal of Nanomedicine & Nanotechnology

Author(s): Xu Y, Meng F, Cheng R, Zhong Z

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Abstract 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(epsilon-caprolactone) (PCL) that contains two lipoyl functional groups at their interface (PEG-L(2)-PCL) has been synthesized. (1)H NMR spectroscopy and gel permeation chromatography (GPC) measurements show that the PEG-L(2)-PCL block copolymer had a controlled composition (PEG 5 kDa and PCL 5.4 kDa) and a polydispersity index (PDI) of 1.36. PEG-L(2)-PCL formed micelles with sizes that ranged from 20 to 150 nm in aqueous solutions, wherein a critical micelle concentration (CMC) of 16 mg.L(-1) 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 10 x 10(-3) 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 10 mg L(-1) (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 ( approximately 80\% release in 0.5 h). In the presence of 10 x 10(-3) 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. This article was published in Macromol Biosci and referenced in Journal of Nanomedicine & Nanotechnology

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