Acrylate-Based Block Copolymers Prepared by Atom Transfer Radical Polymerization as Matrices for Drug Delivery Applications

Abstract

Block copolymers, synthesized by atom transfer radical polymerization (ATRP) processes, were evaluated as drug delivery matrices for the controlled release of paclitaxel (PTX) from coronary stents. The polymers were multi-block copolymers consisting of poly(butyl acrylate) or poly(lauryl acrylate) soft blocks and hard blocks composed of poly(methyl methacrylate), poly(isobornyl acrylate) or poly(styrene) homo or copolymers. The block copolymers had variable elastomeric properties which influenced the stent coating integrity when assessed by SEM imaging of over-expanded stents. In vitro PTX release kinetics from coronary stents coated with these copolymers typically showed an early burst followed by sustained release behavior which permitted the elution of the majority of the PTX over a 10 day time period. It was determined that neither the soft or the hard block appeared to affect the release kinetics of PTX at a loading of 25% drug by weight, whereas some effects were observed at 10% drug loading. DSC analysis showed that the PTX was at least partially miscible with the poly(n-butyl acrylate) phase of these block copolymers. Sterilization stability was evaluated by exposing both the copolymer alone and copolymer/PTX coated stents to e-beam radiation at doses of 25, 50 and 75 kGy. The block copolymers containing segments bearing quaternary carbons within the polymer backbone were found to be less stable to the radiation and showed a decrease in molecular weight as determined by gel permeation chromatography. Whereas, those without quaternary carbons showed no significant change in molecular weight when exposed to the same doses of radiation. There was no significant change in PTX release profile from any of the acrylate-based copolymers after exposure to up to 75 kGy of e-beam radiation, and this was attributed to the inherent radiation stability of the polyacrylate center blocks.