Acid-Labile Core Cross-Linked Micelles for pH-Triggered Release of Antitumor Drugs

Centre for Advanced Macromolecular Design, The University of New South Wales, Sydney 2052, NSW, Australia.
Biomacromolecules (Impact Factor: 5.75). 08/2008; 9(7):1826-36. DOI: 10.1021/bm800043n
Source: PubMed


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.

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    • "e l s e v i e r . c o m / l o c a t e / e u r o p o l j micelles of block polymers were reported using degradable cross-linkers by reversible addition fragmentation transfer (RAFT) polymerization [7] [8]. We have reported core-surface cross-linked nanoparticles by interblock RAFT polymerization of poly(ethylene oxide)-b-polystyrene block copolymer using divinyl benzene as a cross-linker [9]. "
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