Drug-eluting stent coatings based on poly(lactide-co-glycolide) incorporating paclitaxel and cyclosporine A

Abstract

This study was intended to develop stent coating based on the biocompatible polymer and drugs. Polymer stents showed antiproliferative effects on smooth muscle cells (SMC) by using paclitaxel and cyclosporine A at clinically relevant doses. In this study, absorbable polymer stent coatings for localized drug delivery based on poly(lactide-co-glycolide) (PLGA), paclitaxel (Px) and cyclosporine A (CsA) were developed. Metallic stents were coated with applicable compositions of PLGA/Drug. Coated stent had top coating by polyurethane. A bi-layer system, with two different polymer in PLGA and PU, was used in the study, to simulate drug released from a fully biodegradable multilayer polymer stent. The specimens were used to assess the drug release kinetics with HPLC. Mechanical integrity of the stent coatings was studied with scanning electron microscopy. The interconnection of the coated stents with a balloon-catheter was characterized by the measurement of stent dislodgment force. The release of drug was established over time periods up to 24 days in sodium chloride solution. The maintenance of the mechanical integrity of the polymer coating during crimping and dilation of the specimens could be verified, and a sufficient stent dislodgment force of 0.8N was measured.;본 연구에 의해 두 가지 약물의 용출시간을 지속시켜서 세포주기에 맞추어 독립적으로 속방출 내지 서방출 될 수 있고 지속적으로 약효를 낼 수 있으며 안정한 형태의 약물 코팅 스텐트 개발을 목적으로 하였다. 전기분사 방법(electrospray)을 이용하여 혈관 평활근 세포의 증식과 이동을 억제하는 효과가 있는 paclitaxel과 면역억제제인 cyclosporine A의 혼합용액을 분사하였으며 침지 코팅 방법(dipcoating)을 이용하여 폴리우레탄을 탑 코팅 하였다. 약물용출패턴과 스텐트의 기계적 물성을 시험하였다. 실험 결과 안정한 형태의 약물 코팅 스텐트임이 확인 되었고 본 실험으로 개발된 스텐트의 국소 전달요법(local drug delivery)을 이용하여 전신독성 없이 약물을 관상동맥 내로 국소 투여하여 관상동맥 스텐트 재협착에 대한 예방 효과를 기대할 수 있다.