Journal
MOLECULAR PHARMACEUTICS
Volume 14, Issue 3, Pages 799-807Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.6b01051
Keywords
drug delivery system; core cross-linked micelles; amphiphilic linear-hyperbranched copolymer; reduction and pH dual-responsive; controlled release
Funding
- Program for New Century Excellent Talents in University of the Ministry of Education [NCET-09-0441]
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Novel strategy has been developed for fabricating the biocompatible reduction and pH dual-responsive core cross-linked (CCL) micelles as drug delivery system (DDS) for the controlled anticancer drug delivery, via the atom transfer radical polymerization (ATRP) of tert-butyl acrylate (tBA) with N,N'-bis(acryloyl)cystamine (BACy) as cross-linker and a multifunctional amphiphilic linear-hyperbranched copolymer as macro initiator, which was synthesized via the self-condensing vinyl copolymerization (SCVCP) of tBA and p-chloromethylstyrene (CMS) with a poly(ethylene glycol) (PEG) based initiator (mPEG-Br). The hydrolyzed core cross-linked (HCCL) micelles were obtained as DDS for doxorubicin (DOX) by hydrolysis the tBA units into acrylic acid (AA) ones. The in vitro release performance showed that higher GSH concentration and/or lower pH value would lead to a faster and more efficient DOX release, meaning their reduction and pH dual responsiveness. Therefore, the proposed HCCL micelles are expected to be potential anticancer drug-carriers for tumor microenvironment responsive controlled delivery.
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