期刊
JOURNAL OF DRUG TARGETING
卷 21, 期 10, 页码 981-993出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/1061186X.2013.831421
关键词
Core-shell morphology; doxorubicin; nanogel; PEG-b-poly(L-glutamic acid); phenylalanine
资金
- National Institutes of Health [CA116590]
- Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health [P20GM103480]
Polymer nanogels have gained considerable attention as a potential platform for drug delivery applications. Here we describe the design and synthesis of novel polypeptide-based nanogels with hydrophobic moieties in the cross-linked ionic cores. Diblock copolymer, poly(ethylene glycol)-b-poly(L-glutamic acid), hydrophobically modified with L-phenylalanine methyl ester moieties was used for controlled template synthesis of nanogels with small size (ca. 70nm in diameter) and narrow particle size distribution. Steady-state and time-resolved fluorescence studies using coumarin C153 indicated the existence of hydrophobic domains in the ionic cores of the nanogels. Stable doxorubicin-loaded nanogels were prepared at high drug capacity (30 w/w%). We show that nanogels are enzymatically-degradable leading to accelerated drug release under simulated lysosomal acidic pH. Furthermore, we demonstrate that the nanogel-based formulation of doxorubicin is well tolerated and exhibit an improved antitumor activity compared to a free doxorubicin in an ovarian tumor xenograft mouse model. Our results signify the point to a potential of these biodegradable nanogels as attractive carriers for delivery of chemotherapeutics.
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