title: Preparation of Polymeric Prodrug Paclitaxel-Poly(lactic acid)-b-Polyisobutylene and Its Application in Coatings of a Drug Eluting Stent.
abstract: To develop a novel biodegradable and quite adhesive coating material for fabricating a paclitaxel (PTX)-containing eluting stent, herein, we report two kinds of drug eluting stent (DES) materials. One of them is a prodrug, PTX end-capped poly(lactic acid)-b-polyisobutylene (PTX-PLA-b-PIB) diblock copolymer, which possesses favorable biodegradability and biocompatibility. The other is a mixture of PIB-b-PLA diblock copolymer and PTX. PIB-b-PLA was synthesized via the ring-opening polymerization (ROP) using hydroxyl-terminated polyisobutylene (PIB-OH) as the initiator, while the PTX-PLA-b-PIB prodrug was prepared through a combination of ROP and Cu(I)-catalyzed azide-alkyne cycloaddition "click" reaction. The chemical structures and compositions as well as the molecular weights and molecular weight distributions of these copolymers have been fully characterized by (1)H nuclear magnetic resonance, Fourier transform infrared, and gel permeation chromatography measurements. The thermal degradation behavior and glass transition temperature (Tg) of the copolymers were studied by thermogravimetric analysis and differential scanning calorimetry, respectively. The solutions of PTX-PLA-b-PIB and the PIB-b-PLA/PTX mixture were separately coated onto the bare metal stents to form the PTX-containing DES. Subsequently, the surface structures and morphologies of the bare stent and DES were studied by atomic force microscopy and scanning electron microscopy, respectively. The in vitro release of PTX from these stents was conducted in a buffer medium (PBS 7.4) at 37 °C. The results showed that the coating formed by a blend of PTX-PLA-b-PIB, PIB-b-PLA, and PTX yielded a release that was better sustained than those of the individual PTX-PLA-b-PIB prodrug or PIB-b-PLA/PTX mixture. MTT assays demonstrated that the stent coated with PTX-PLA-b-PIB displayed a cytotoxicity lower than that of the PIB-b-PLA/PTX mixed layer, and the biocompatibility of coatings can be effectively improved by the prodrug.
authors.affiliation: †College of Chemistry, Chemical Engineering and Materials Science, Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Soochow University, Suzhou 215123, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Ren
authors.affiliation: †College of Chemistry, Chemical Engineering and Materials Science, Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Soochow University, Suzhou 215123, China.
authors.forename: Mingzu
authors.initials: M
authors.lastname: Zhang
authors.affiliation: †College of Chemistry, Chemical Engineering and Materials Science, Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Soochow University, Suzhou 215123, China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: He
authors.affiliation: ‡State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Wu
authors.affiliation: †College of Chemistry, Chemical Engineering and Materials Science, Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Soochow University, Suzhou 215123, China.
authors.forename: Peihong
authors.initials: P
authors.lastname: Ni
mesh_terms: D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D004058:Diffusion; D004343:Drug Implants / Q000008:administration & dosage / Q000737:chemistry; D054855:Drug-Eluting Stents; D019344:Lactic Acid / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011090:Polyenes / Q000737:chemistry*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry; D050257:Tubulin Modulators / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D004343:Drug Implants; D011090:Polyenes; D011091:Polyesters; D011108:Polymers; D011355:Prodrugs; D050257:Tubulin Modulators; D019344:Lactic Acid; C033616:poly(lactide); C008967:polyisobutylene; D017239:Paclitaxel
keywords: biodegradability; drug delivery; drug eluting stent; paclitaxel; prodrug