期刊
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY
卷 51, 期 2, 页码 347-362出版社
WILEY
DOI: 10.1002/pola.26392
关键词
biomaterials; core-crosslinked micelles; drug delivery systems; interface-crosslinked micelles; micelles; polycarbonate; poly lactic acid
资金
- Department of Defense Prostate Cancer Research Program [W81XWH-10-1-0969]
Our objective was to synthesize and evaluate lactic acid- and carbonate-based biodegradable core- and core-corona crosslinkable copolymers for anticancer drug delivery. Methoxy poly(ethylene glycol)-b-poly(carbonate-co-lactide-co-5-methyl-5-allyloxycarbonyl-1,3-dioxane-2-one) [mPEG-b-P(CB-co-LA-co-MAC)] and methoxy poly(ethylene glycol)-b-poly(acryloyl carbonate)-b-poly(carbonate-co-lactide) [mPEG-b-PMAC-b-P(CB-co-LA)] copolymers were synthesized by ring-opening polymerization of LA, CB, and MAC using mPEG as an macroinitiator and 1,8-diazabicycloundec-7-ene as a catalyst. These amphiphilic copolymers which exhibited low polydispersity and critical micelle concentration values (0.81 mg/L) were used to prepare micelles with or without drug and stabilized by crosslinking via radical polymerization of double bonds introduced in the core and interface to improve stability. mPEG114-b-P(CB8-co-LA35-co-MAC2.5) had a higher drug encapsulation efficiency (78.72% +/- 0.15%) compared to mPEG114-b-PMAC2.5-b-P(CB9-co-LA39) (20.29% +/- 0.11%).1H NMR and IR spectroscopy confirmed successful crosslinking (similar to 70%) while light scattering and transmission electron microscopy were used to determine micelle size and morphology. Crosslinked micelles demonstrated enhanced stability against extensive dilution with aqueous solvents and in the presence of physiological simulating serum concentration. Furthermore, bicalutamide-loaded crosslinked micelles were more potent compared to non-crosslinked micelles in inhibiting LNCaP cell proliferation irrespective of polymer type. Finally, these results suggest crosslinked micelles to be promising drug delivery vehicles for chemotherapy. (c) 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
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