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Controlled release of paclitaxel using a drug-eluting stent through modulation of the size of drug particles in vivo.

Drug-eluting stents (DESs) are generally used in percutaneous coronary intervention. Paclitaxel (PTX) is widely used in DESs to suppress neointima, which causes restenosis. However, the PTX release profile is slow owing to its hydrophobic properties, resulting in negative effects on re-endothelialization in vessels. In this study, we assessed the effects of the controlled release of PTX particles of specific sizes on in-stent restenosis (ISR). PTX particle sizes were controlled by adjusting the evaporating temperature of the solvent from 25 to 80°C during ultrasonic coating, and DESs were prepared. The properties of prepared films and DESs were analyzed, and cell viability was assessed in vitro and in vivo. Poly(lactic-co-glycolic acid) (PLGA)/PTX500-loaded stents showed the most rapid release for 58 days, and smaller drug particles exhibited lower PTX release rates. In vivo, PLGA/PTX50-, PLGA/PTX250-, and PLGA/PTX500-loaded stents showed good efficacy for alleviating ISR as compared with bare metal stents and PLGA/PTX5-loaded stents. However, PLGA/PTX250- and PLGA/PTX500-loaded stents exhibited strut exposure and reduced recovery of the vascular compared with PLGA/PTX50-loaded stents. PTX drug particles of approximately 50 nm were most effective in vivo, and the control of particle size is a promising strategy for improving the performance of PTX-eluting stents. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2275-2283, 2018.