Controlled Delivery of Paclitaxel from Stent Coatings Using Poly(hydroxystyrene-b-isobutylene-b-hydroxystyrene) and Its Acetylated Derivative

Abstract

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.

Paclitaxel delivery from cobalt-chromium alloy surfaces using self-assembled monolayers

“…Tween-20, a nonionic surfactant, was added to the PBS to increase the solubility of PAT and to maintain sink conditions. [25][26][27][28] At predetermined time points ͑1, 3, 5, 7, 14, 21, 28, and 35 days͒, the alloy samples were taken out of the incubated PBS/T-20 solution and immediately transferred to fresh PBS/T-20 solution for the next time point. The PBS/T-20 solutions collected at each time point were then used to calculate the amount of drug released using high performance liquid chromatography ͑HPLC͒.…”

Quantitative spatial distribution of sirolimus and polymers in drug‐eluting stents using confocal Raman microscopy

“…[2][3][4][5][6] In the few cases examined, the strategies for modifying elution profiles relied on changing the drug loading relative to polymer, changing the physical, and mechanical properties of the polymer matrix, or creating reservoir or degradable systems. 5,7 The description of the solidstate distribution of drug was also exclusive to surface characterization and neglected to describe the distribution within the three-dimensional polymer matrix.…”

“…Atomic force microscopy (AFM) and scanning electron microscopy (SEM) are both routinely used to characterize the physical attributes of stent coatings. [2][3][4]6,[11][12][13][14] AFM is useful for physical descriptions such as surface topography and identifying component domains. SEM is useful to describe the coating conformity to the stent pre-and post-expansion.…”

Reduced Burst Release from ePTFE Grafts: A New Coating Method for Controlled Drug Release

“…This result is similar to the release pattern of TAXUS, which is a paclitaxel eluting stent with a variety of ratios of PTx to polymer. 16,17 However, high concentrations of paclitaxel are locally toxic and may cause necrosis. 18 In order to develop a slow and controlled release, coating experimental that varied in dipping time and number were performed.…”

“…To verify the effect of double coating, a drug eluting graft was incubated in PBS-tween buffer at 37 °C with vigorous shaking. 16 The different initial burst and release patterns, with the same drug loaded onto the graft, are shown in Figure 3. Paclitaxel loaded grafts using single dipping with a solution of 0.5 mg/mL contained drug of 0.388 μg/ mm 2 and those using double coating method dipped twice into 0.3 mg/mL for a similar drug contents and contained 0.380 μg/mm 2 .…”