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  • Title: Novel reduction-sensitive micelles for triggered intracellular drug release.
    Author: Sun P, Zhou D, Gan Z.
    Journal: J Control Release; 2011 Oct 10; 155(1):96-103. PubMed ID: 21075151.
    Abstract:
    Novel reduction-sensitive micelles based on poly(ethylene oxide)-b-poly(N-methacryloyl-N'-(t-butyloxycarbonyl)cystamine) (PEO-b-PMABC) diblock copolymers were developed and applied for triggered intracellular drug release. PEO-b-PMABC block copolymers were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of MABC with dithioester-capped PEO as macroRAFT agent. Gel permeation chromatography (GPC) and (1)H NMR analysis showed that the copolymers have controlled compositions and molecular weights, indicating the living nature of polymerization. These copolymers were self-assembled into micelles. The physicochemical characteristics and reduction-sensitivity of the resultant micelles were investigated by fluorescence measurement, transmission electron microscopy (TEM), and dynamic light scattering (DLS). The results showed that PEO-b-PMABC micelles are stable at normal physiologic condition but readily cleaved into free copolymers under reducing environment. In vitro release of doxorubicin (DOX) and cell experiments showed that the drug-loaded PEO-b-PMABC micelles accomplished much faster drug release under reducing condition and higher anticancer efficacy as compared to the control without reduction-sensitivity, indicating great potential of PEO-b-PMABC micelles for efficient intracellular drug delivery.
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