Synthesis, Properties, and Applications of Carboxylic Acid Functionalized Polyisobutylene

Polyisobutylene (PIB) and its copolymers are used in a wide range of commercial products owing to their high chemical stability, impermeability, elasticity, and biocompatibility. In this thesis, linear and arborescent PIB containing small percentages of isoprene (IP) were functionalized to provide different derivatives and their physical and biological properties were studied

Polyisobutylene-paclitaxel conjugates with pendant carboxylic acids and polystyrene chains: Towards multifunctional stent coatings with slow drug release

Drug-eluting stents are used in the treatment of atherosclerosis, where the incorporation of anti-proliferative or anti-inflammatory drugs decreases the rate of restenosis, the recurrence of artery narrowing. However, these stents can suffer from limitations such as drug depletion and delamination of the drug-eluting coating from the stent surface. Described here is an approach aimed at addressing these issues. Starting from a maleic anhydride adduct of polyisobutylene (PIB) prepared from butyl rubber, ring opening using paclitaxel (PTX) or a combination of PTX and polystyrene (PS) afforded covalent conjugates of PTX and PIB or PIB-PS graft copolymers bearing pendant carboxylic acids. When coated on stainless steel, the drug release was slower than that from a control coating that ressembles a clinical formulation comprising a physical mixture of a PS-PIB-PS triblock copolymer (SIBS) and PTX. The PTX conjugates also exhibited enhanced adhesion to stainless steel and increased tensile strength in comparison with the starting rubber. Cytotoxicity assays indicated that the materials did not leach toxic levels of PTX into cell culture media. Nevertheless, they were capable of inhibiting the adhesion and proliferation of C2C12 cells on their surfaces. These properties are advantageous for the potential application of the materials as stent coatings

Carboxylic acid-functionalized butyl rubber: Synthesis, characterization, and physical properties

© 2015 American Chemical Society. Polyisobutylene (PIB) and other PIB-based materials are of significant interest for a vast array of applications, but chemical modification is often required to obtain the desired properties. Described here are two new approaches for the preparation of carboxylic acid-functionalized PIB. The ring opening of cyclic anhydrides from an allylic alcohol derivative of butyl rubber and the atom transfer radical polymerization of tert-butyl methacrylate from a rubber derivative both ultimately afford carboxylated materials. These materials displayed significantly enhanced adhesion to stainless steel, as well as increased ultimate tensile strength and Young\u27s modulus in comparison to unmodified rubbers. Rheological studies suggested that they exhibit a greater degree of cross-linking-type behavior than the parent butyl rubber. Combined, these studies suggest that the properties of PIB can be readily tuned through synthetic modifications of the backbone, even at low mole percent, and that carboxylic acid moieties can impart desirable properties for various applications

Synthesis and properties of arborescent polyisobutylene derivatives and a paclitaxel conjugate: Towards stent coatings with prolonged drug release

© 2015 Elsevier Ltd. All rights reserved. Polyisobutylene (PIB) and its copolymers are used in a wide range of commercial products owing to their high chemical stability, impermeability, elasticity, and biocompatibility. The development of arborescent PIB (arb-PIB) opens many new possibilities for tuning PIB\u27s properties and for introducing new functionalities. In this work, arb-PIB with short isoprene-rich terminal sequences (arb-PIB-co-IP) was functionalized to provide arborescent epoxide, allylic alcohol, and carboxylic acid derivatives of PIB. The carboxylic acid derivative was used to conjugate the antiproliferative agent paclitaxel (PTX) for investigation as a potential vascular stent coating. The thermal, tensile, and rheological properties of all of the functionalized arb-PIB materials were studied and compared to their linear analogues in order to gain insight into the effects of polymer architecture on these properties as well as to determine their suitability as potential medical device coatings. A coating using the PTX conjugate was found to release PTX much more slowly than control formulations with physically encapsulated drug, yet was still able to prevent cell adhesion and proliferation on their surfaces

Covalent Polyisobutylene-Paclitaxel Conjugates for Controlled Release from Potential Vascular Stent Coatings

© 2015 American Chemical Society. 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