Regulation of smooth muscle cell proliferation using paclitaxel-loaded poly(ethylene oxide)-poly(lactide/glycolide) nanospheres.
Available data suggest that drugs should be delivered to a vascular lesion at a high concentration over an extended period of time to control vascular smooth muscle cell (VSMC) proliferation. This study was undertaken to formulate a paclitaxel, an antimicrotubule agent, into a biodegradable poly (ethylene oxide)-poly(lactide/glycolide) (PEO-PLGA) nanosphere as a sustained drug delivery system and to study its effects on VSMC in culture. The paclitaxel-loaded nanospheres (PT/NS), prepared by an emulsion-solvent evaporation method, had an average diameter of approximately 150 nm and showed a sustained release profile over 4 weeks. The PT/NS exhibited antiproliferative effects comparable to those observed with free paclitaxel. The cellular internalization of nanospheres was visualized using confocal fluorescence microscopy, and from a flow cytometry study the progressive cellular uptake profile, uptake inhibition at low temperature, and saturation uptake kinetics (concentration dependency) were observed. These suggest that (adsorptive) pinocytosis is a major uptake mechanism of the nanospheres. The sustained drug release profile and cellular internalization results suggest that nanospheres loaded with paclitaxel may potentially be used as an endocytizable, local sustained drug delivery system for the prevention of restenosis.
Department of Pharmaceutics and Pharmaceutical Chemistry/Center for Controlled Chemical Delivery, University of Utah, Salt Lake City 84112-9452, USA.
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Jeong
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Rathi
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Kim
D000818:Animals; D001672:Biocompatible Materials; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D019344:Lactic Acid; D018613:Microscopy, Confocal; D008863:Microspheres; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D017239:Paclitaxel; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers
D001672:Biocompatible Materials; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D017239:Paclitaxel