Acid-labile core cross-linked micelles for pH-triggered release of antitumor drugs.
Micelles of a model amphiphilic block copolymer, poly(hydroxyethyl acrylate)-block-poly(n-butyl acrylate) (PHEA-b-PBA), synthesized via the RAFT polymerization were cross-linked by copolymerization of a degradable cross-linker from the living RAFT-end groups of PBA chains, yielding a cross-linked core without affecting significantly the original micelle size. The cross-linker incorporation into the micelles was evidenced via physicochemical analysis of the copolymer unimers formed upon acidic cleavage of the cross-linked micelles. High doxorubicin loading capacities (60 wt %) were obtained. Hydrolysis of less than half of the cross-links in the core was found to be sufficient to release doxorubicin faster at acidic pH compared to neutral pH. The system represents the first example of core-cross-linked micelles that can be destabilized (potentially both above and below CMC) by the pH-dependent cleavage of the cross-links and the subsequent polarity change in the core to enable the release of hydrophobic drugs entrapped inside the micelle.
Centre for Advanced Macromolecular Design, The University of New South Wales, Sydney 2052, NSW, Australia.
Yannie
Y
Chan
To
T
Wong
Frances
F
Byrne
Maria
M
Kavallaris
Volga
V
Bulmus
D000179:Acrylates; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008823:Micelles; D011102:Polyhydroxyethyl Methacrylate / Q000031:analogs & derivatives; D011108:Polymers
D000179:Acrylates; D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D008823:Micelles; D011108:Polymers; C498324:poly(n-butyl acrylate); D011102:Polyhydroxyethyl Methacrylate; C023037:poly(2-hydroxyethyl acrylate); D004317:Doxorubicin