title: Covalent Polyisobutylene-Paclitaxel Conjugates for Controlled Release from Potential Vascular Stent Coatings.
abstract: The development of covalent polyisobutylene (PIB)-paclitaxel (PTX) conjugates as a potential approach to controlling drug release from vascular stent coatings is described. PIB-PTX materials containing ∼24 and ∼48 wt % PTX, conjugated via ester linkages, were prepared. The PTX release profiles were compared with those of physical mixtures of PTX with carboxylic acid-functionalized PIB and with the triblock copolymer polystyrene-b-PIB-b-polystyrene (SIBS). Covalent conjugation led to significantly slower drug release. Atomic force microscopy imaging of coatings of the materials suggested that the physical mixtures exhibited multiple domains corresponding to phase separation, whereas the materials in which PTX was covalently conjugated appeared homogeneous. Coatings of the conjugated materials on stainless steel surfaces suffered less surface erosion than the physically mixed materials, remained intact, and adhered well to the surface throughout the thirty-five day study. Tensile testing and rheological studies suggested that the incorporation of PTX into the polymer introduces similar physical changes to the PIB as the incorporation of a glassy polystyrene block does in SIBS. Cytotoxicity assays showed that the coatings did not release toxic levels of PTX or other species into a cell culture medium over a 24 h period, yet the levels of PTX in the materials were sufficient to prevent C2C12 cells from adhering to and proliferating on them. Overall, these results indicate that covalent PIB-PTX conjugates have promise as coatings for vascular stents.
authors.affiliation: †Department of Chemistry, University of Western Ontario, 1151 Richmond Street, London N6A 5B7, Canada.
authors.forename: John F
authors.initials: JF
authors.lastname: Trant
authors.affiliation: †Department of Chemistry, University of Western Ontario, 1151 Richmond Street, London N6A 5B7, Canada.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: McEachran
authors.affiliation: ‡Department of Chemical and Biochemical Engineering, The University of Western Ontario, 1151 Richmond Sreet, London N6A 5B9, Canada.
authors.forename: Inderpreet
authors.initials: I
authors.lastname: Sran
authors.affiliation: §Biomedical Engineering Graduate Program, The University of Western Ontario, 1151 Richmond Street, London N6A 5B9, Canada.
authors.forename: Bethany A
authors.initials: BA
authors.lastname: Turowec
authors.affiliation: ∥Department of Physics and Astronomy, The University of Western Ontario, 1151 Richmond Street, London N6A 5B7, Canada.
authors.forename: John R
authors.initials: JR
authors.lastname: de Bruyn
authors.affiliation: †Department of Chemistry, University of Western Ontario, 1151 Richmond Street, London N6A 5B7, Canada.|‡Department of Chemical and Biochemical Engineering, The University of Western Ontario, 1151 Richmond Sreet, London N6A 5B9, Canada.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Gillies
mesh_terms: D000818:Animals; D002460:Cell Line; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D054855:Drug-Eluting Stents; D008422:Materials Testing; D051379:Mice; D017239:Paclitaxel / Q000737:chemistry* / Q000493:pharmacokinetics*; D011090:Polyenes / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D011090:Polyenes; D011108:Polymers; C008967:polyisobutylene; D017239:Paclitaxel
keywords: SIBS; arterial stent; butyl rubber; coatings; controlled drug release; paclitaxel; polyisobutylene