Evaluation of Acrylate-Based Block Copolymers Prepared by Atom Transfer Radical Polymerization as Matrices for Paclitaxel Delivery from Coronary Stents

Abstract

Acrylate-based block copolymers, synthesized by atom transfer radical polymerization (ATRP) processes, were evaluated as drug delivery matrices for the controlled release of paclitaxel from coronary stents. The polymers were multiblock 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. Depending on the ratio of hard to soft blocks in the copolymers, coating formulations were produced that possessed variable elastomeric properties, resulting in stent coatings that maintained their integrity when assessed by scanning electron microscopy (SEM) imaging of overexpanded stents. In vitro paclitaxel 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 paclitaxel over a 10-day time period. It was determined that neither the nature of the polyacrylate (n-butyl or lauryl) nor that of the hard block appeared to affect the release kinetics of paclitaxel at a loading of 25% drug by weight, whereas some effects were observed at lower drug loading levels. Differential scanning calorimetry (DSC) analysis indicated that the paclitaxel was at least partially miscible with the poly(n-butyl acrylate) phase of those block copolymers. The copolymers were also evaluated for sterilization stability by exposing both the copolymer alone and copolymer/paclitaxel coated stents to e-beam radiation at doses of 1-3 times the nominal dose used for medical device sterilization (25 kGy). It was found that the copolymers containing blocks bearing quaternary carbons within the polymer backbone were less stable to the radiation and showed a decrease in molecular weight as determined by gel-permeation chromatography. Conversely, those without quaternary carbons showed no significant change in molecular weight when exposed to 3 times the standard radiation dose. There was no significant change in drug release profile from any of the acrylate-based copolymers after exposure to 75 kGy of e-beam radiation, and this was attributed to the inherent radiation stability of the poly(n-butyl acrylate) center block.

Blends of Paclitaxel with POSS-Based Biodegradable Polyurethanes: Morphology, Miscibility, and Specific Interactions

“…Richard et al reported that paclitaxel preferentially resides in the poly(n-butyl acrylate) (PBA) phase of poly(methyl methacrylate-block-n-butyl acrylate-block-methyl methacrylate) (PMMA-b-PBA-b-PMMA)) triblock copolymers. 23 In contrast, Cho et al found that the paclitaxel segregated to the PMMA phase in the triblock copolymer of poly(methyl methacrylate-b-isobutylene-b-methyl methacrylate) (PMMA-b-PIB-b-PMMA). 8 The apparent discrepancy between these findings confirms the importance of the interactions between the paclitaxel and different blocks in controlling drug distribution.…”

“…Therefore, it is expected that the amorphous paclitaxel will act as an antiplasticizer and enhance the T g of molecularly miscible polymeric formulations when the pure polymer T g is lower than the drug T g . Cho et al 8 and Richard et al 23 observed a continuous increment of T g with increasing paclitaxel concentration *To whom correspondence should be addressed. E-mail: ptmather@ syr.edu.…”

Water Vapour Permeability and Wet Rub Fastness of Finished Leathers - Effect of Acrylic Polymer Dispersion Formulations

“…A free radical polymerization has three principal steps which include: the initiation of the active monomer, propagation or growth of the active (or free radical) chain by sequential addition of monomers, and termination of the active chain to give the final polymer product. Acrylate based block copolymes have been synthesized by atom transfer radical polymerization (ATRP) process [10]. The polymers were multiblock copolymers consisting of poly(butyl acrylate) or poly(lauryl acrylate) soft Acrylic Polymer Dispersion Formulations blocks and hard blocks composed of poly (methymethacrylate), poly (isoborny acrylate), or poly (styrene) homo-or copolymers.…”

Controlled delivery of paclitaxel from stent coatings using novel styrene maleic anhydride copolymer formulations

“…9 For hydrophobic drugs like PTx, it has been shown that release from a stent coating can be modulated effectively by changing the drug loading, introducing excipients, or through blending with other homopolymers or copolymers. [10][11][12] Conventional techniques, such as differential scanning calorimetry (DSC), have been used to evaluate potential drug-polymer interactions and better understand the characteristics of the polymer carrier that control the release of PTx. [13][14][15][16][17] Atomic force microscopy (AFM) is a technique that has proven useful for examining the morphology of stent coatings.…”

“…Correlation of AFM images with specific drug release profiles has enhanced the understanding of the PTx-based stent coating systems. [9][10][11][12]18 Similar studies with novel polymeric drug-delivery coatings that exhibit different release profiles can expand the understanding of drug distribution, interactions, and subsequent release from the coating.…”