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Biomacromolecules. 2013 Oct 14;14(10):3697-705. doi: 10.1021/bm4010518. Epub 2013 Oct 3.

Evaluation of doxorubicin-loaded 3-helix micelles as nanocarriers.

Author information

1
Department of Materials Science and Engineering, University of California , Berkeley, California 94720, United States.

Abstract

Designing stable drug nanocarriers, 10-30 nm in size, would have significant impact on their transport in circulation, tumor penetration, and therapeutic efficacy. In the present study, biological properties of 3-helix micelles loaded with 8 wt % doxorubicin (DOX), ~15 nm in size, were characterized to validate their potential as a nanocarrier platform. DOX-loaded micelles exhibited high stability in terms of size and drug retention in concentrated protein environments similar to conditions after intravenous injections. DOX-loaded micelles were cytotoxic to PPC-1 and 4T1 cancer cells at levels comparable to free DOX. 3-Helix micelles can be disassembled by proteolytic degradation of peptide shell to enable drug release and clearance to minimize long-term accumulation. Local administration to normal rat striatum by convection enhanced delivery (CED) showed greater extent of drug distribution and reduced toxicity relative to free drug. Intravenous administration of DOX-loaded 3-helix micelles demonstrated improved tumor half-life and reduced toxicity to healthy tissues in comparison to free DOX. In vivo delivery of DOX-loaded 3-helix micelles through two different routes clearly indicates the potential of 3-helix micelles as safe and effective nanocarriers for cancer therapeutics.

PMID:
24050265
PMCID:
PMC3923314
DOI:
10.1021/bm4010518
[Indexed for MEDLINE]
Free PMC Article

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