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.
Chan
Yannie
Y
Centre for Advanced Macromolecular Design, The University of New South Wales, Sydney 2052, NSW, Australia.
Wong
To
T
Byrne
Frances
F
Kavallaris
Maria
M
Bulmus
Volga
V
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