Controlled delivery of paclitaxel from stent coatings using poly(hydroxystyrene-b-isobutylene-b-hydroxystyrene) and its acetylated derivative.
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.
Sipos
Laszlo
L
Polymer Science Program, Department of Chemistry, University of Massachusetts Lowell, One University Avenue, Lowell, Massachusetts 01854, USA.
Som
Abhijit
A
Faust
Rudolf
R
Richard
Robert
R
Schwarz
Marlene
M
Ranade
Shrirang
S
Boden
Mark
M
Chan
Ken
K
D000042:Absorption; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry*; D001704:Biopolymers / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002412:Cations; D002851:Chromatography, High Pressure Liquid; D003510:Cyclohexanes / Q000737:chemistry; D016503:Drug Delivery Systems; D005030:Ethylenes / Q000737:chemistry; D006868:Hydrolysis; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D008970:Molecular Weight; D009942:Organometallic Compounds; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D012833:Siloxanes / Q000737:chemistry*; D012997:Solvents; D015607:Stents; D020058:Styrene / Q000737:chemistry; D013343:Styrenes / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors; D014025:Titanium / Q000737:chemistry
C506477:4-(tert-butyldimethylsiloxy)styrene; D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D001704:Biopolymers; D002412:Cations; D003510:Cyclohexanes; D005030:Ethylenes; D009942:Organometallic Compounds; D011108:Polymers; D012833:Siloxanes; D012997:Solvents; D013343:Styrenes; C500040:poly(styrene-b-isobutylene-b-styrene); D020058:Styrene; C102815:titanium isopropoxide; C036216:ethylene; D014025:Titanium; D017239:Paclitaxel