A poly(styrene-b-isobutylene-b-styrene) (SIBS) triblock polymer is employed as the polymer drug carrier for the TAXUS Express2 Paclitaxel-Eluting Coronary Stent system (Boston Scientific Corp.). It has been shown that the release of paclitaxel (PTx) from SIBS can be modulated by modification of either drug-loading ratio or altering the triblock morphology by blending. In the present work, results toward achieving release modulation of PTx by chemical modification of the styrenic portion (using hydroxystyrene or its acetylated version) of the SIBS polymer system are reported. The synthesis of the precursor poly[(p-tert-butyldimethylsilyloxystyrene)]-b-isobutylene-b-[(p-tert-butyldimethylsilyloxystyrene] triblock copolymers was accomplished by living sequential block copolymerization of isobutylene (IB) and p-(tert-butyldimethylsiloxy)styrene (TBDMS) utilizing the capping-tuning technique in a one-pot procedure in methylcyclohexane/CH3Cl at -80 degrees C. This procedure involved the living cationic polymerization of IB with the 5-tert-butyl-1,3-bis(1-chloro-1-methylethyl)benzene/TiCl4 initiating system and capping of living difunctional polyisobutylene (PIB) chain ends with 1,1-ditolylethylene (DTE) followed by addition of titanium(IV) isopropoxide (Ti(OIp)4) to lower the Lewis acidity before the introduction of TBDMS. Deprotection of the product with tetrabutylammonium fluoride yielded poly(hydroxystyrene-b-isobutylene-b-hydroxystyrene), which was quantitatively acetylated to obtain the acetylated derivative. The hydroxystyrene and acetoxystyrene triblock copolymers have acceptable mechanical properties for use as drug delivery coatings for coronary stent applications. It was concluded that the hydrophilic nature of the endblocks and polarity effects on the drug/polymer miscibility lead to enhanced release of PTx from these polymers. The drug-polymer miscibility was confirmed by differential scanning calorimetry and atomic force microscopy evaluations.
Polyisobutylene (PIB)-based block copolymers have attracted significant interest as biomaterials. Poly(styrene-b-isobutylene-b-styrene) (SIBS) has been shown to be vascularly compatible and, when loaded with paclitaxel (PTx) and coated on a coronary stent, has the ability to deliver the drug directly to arterial walls. Modulation of drug release from this polymer has been achieved by varying the drug/polymer ratio, by blending SIBS with other polymers, and by derivatizing the styrene end blocks to vary the hydrophilicity of the copolymer. In this paper, results are reported on the synthesis, physical properties, and drug elution profile of PIB-based block copolymers containing methacrylate end blocks. The preparation of PIB-poly(alkyl methacrylate) block copolymers has been accomplished by a new synthetic methodology using living cationic and anionic polymerization techniques. 1,1-Diphenylethylene end-functionalized PIB was prepared from the reaction of living PIB and 1,4-bis(1-phenylethenyl)benzene, followed by the methylation of the resulting diphenyl carbenium ion with dimethylzinc (Zn(CH(3))(2)). PIB-DPE was quantitatively metalated with n-butyllithium in tetrahydrofuran, and the resulting macroinitiator could initiate the polymerization of methacrylate monomers, yielding block copolymers with high blocking efficiency. Poly(methyl methacrylate-b-isobutylene-b-methyl methacrylate) (PMMA-b-PIB-b-PMMA) and poly(hydroxyethyl methacrylate-b-isobutylene-b-hydroxyethyl methacrylate) (PHEMA-b-PIB-b-PHEMA) triblock copolymers were synthesized and used as drug delivery matrixes for coatings on coronary stents. The PMMA-b-PIB-b-PMMA/PTx system displayed zero-order drug release, while stents coated with PHEMA-b-PIB-b-PHEMA/PTx formulations exhibited a significant initial burst release of PTx. Physical characterization using atomic force microscopy and differential scanning calorimetry of the formulated PMMA-b-PIB-b-PMMA coating matrix indicated the partial miscibility of PTx with the PMMA microphase of the matrix.
The TAXUS Express 2 Paclitaxel Eluting Coronary Stent System employs a coating consisting of the thermoplastic elastomer, poly(styrene-b-isobutylene-b-styrene; SIBS), selected for its drug-eluting characteristics, vascular compatibility, mechanical properties, and biostability. This study was conducted to evaluate the impact of different SIBS (17-51 mole % styrene) compositions on mechanical properties, chemical stability, and vascular compatibility. Mechanical property (stress-strain measurements) and stability studies were conducted on polymer films with five different styrene contents (17, 24, 32, 39, and 51 mole %). The ultimate tensile strength did not change significantly with composition, but the elongation at break decreased with increased styrene content. A pulsatile fatigue test further confirmed the mechanical stability of SIBS up to 39 mole % styrene. The vascular compatibility of five different SIBS compositions was assessed using SIBS-only coated stents, in the coronary and carotid arteries in a porcine model study. The stability of the vessel wall, rate/degree of endothelialization, inflammation, and thrombus at timepoints from 30 to 180 days were evaluated. The results confirm vascular compatibility over the range of 17-51 mole % styrene.
Surface topography of medical implants provides an important biophysical cue on guiding cellular functions at the cell-implant interface. However, few techniques are available to produce polymeric coatings with controlled microtopographies onto surgical implants, especially onto implant devices of small dimension and with complex structures such as drug-eluting stents. Therefore, the main objective of this study was to develop a new strategy to fabricate polymeric coatings using an electrospraying technique based on the uniqueness of this technique in that it can be used to produce a mist of charged droplets with a precise control of their shape and dimension. We hypothesized that this technique would allow facile manipulation of coating morphology by controlling the shape and dimension of electrosprayed droplets. More specifically, we employed the electrospraying technique to coat a layer of biodegradable polyurethane with tailored microtopographies onto commercial coronary stents. The topography of such stent coatings was modulated by controlling the ratio of round to stretched droplets or the ratio of round to crumped droplets under high electric field before deposition. The shape of electrosprayed droplets was governed by the stability of these charged droplets right after ejection or during their flight in the air. Using the electrospraying technique, we achieved conformal polymeric coatings with tailored microtopographies onto conductive surgical implants. The approach offers potential for controlling the surface topography of surgical implant devices to modulate their integration with surrounding tissues.
Functional aspects of the styrene-b-isobutylene-b-styrene triblock copolymer (SIBS) which is incorporated into a drug-eluting stent (DES) coating are described. The SIBS copolymer is employed on the TAXUS Paclitaxel-Eluting Coronary Stent as a carrier for paclitaxel (PTx). Optical and scanning electron microscopic analysis of stents explanted from rabbit and porcine models after 2 years and 6 months, respectively, showed that the SIBS coating maintained physical integrity. Gel permeation chromatography (GPC) of the copolymer extracted from the coating verified that no polymer degradation occurred over the same period of time. The coating on TAXUS Stents was shown to maintain physical integrity after 400 million cycles of pulsatile or mechanical (tensile) fatigue, simulating 10 years real time use. Inspection of the samples compared to untested controls showed no change in the coating under these cyclic simulated conditions. Films prepared with the same formulation found on TAXUS Stents maintained mechanical strength and resistance throughout the time of testing. Intentional defects introduced into the stent coating were shown to have only a minimal impact on PTx release. These data support the suitability of the SIBS copolymer as a drug carrier for DES applications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.