Controlled Release of Antiproliferative Drugs From Polymeric Systems for Stent Applications and Local Cancer Treatment

Abstract

Restenosis (re‐narrowing of the blood vessel wall) and cancer are two different pathologies that have drawn extensive research attention over the years. Antiproliferative drugs such as paclitaxel inhibit cell proliferation and are therefore effective in the treatment of cancer as well as neointimal hyperplasia, which is known to be the main cause of restenosis. Drug‐eluting stents (DES) significantly reduce the incidence of in‐stent restenosis (ISR), which was once considered a major adverse outcome of percutaneous coronary stent implantations. Localized release of antiproliferative drugs interferes with the pathological proliferation of vascular smooth muscle cells (VSMC), which is the main cause of ISR. Conventional approaches to treating cancer are mainly surgical excision, irradiation, and chemotherapy. In cancer therapy, surgical treatment is usually performed on patients with a resectable carcinoma. An integrated therapeutic approach, such as the addition of a delivery system loaded with an antiproliferative drug at the tumor resection site, is desirable. This will provide a high local concentration of a drug, that is, detrimental to malignant cells which may have survived surgery, thus preventing re‐growth and metastasis of the tumor. The present review describes recent advances in systems for controlled release of antiproliferative agents. It describes basic concepts in drug delivery systems and antiproliferative drugs and then focuses on both types of systems: stents with controlled release of antiproliferative agents, and drug‐eluting particles and implants for local cancer treatment. The last part of this article is dedicated to our novel drug‐eluting composite fiber structures, which can be used as basic stent elements as well as for local cancer treatment.

Promoting Endothelialization of Polymeric Cardiovascular Biomaterials

“…This over proliferation of the smooth muscle cells can also results in narrowing of the luminal area and failure of the graft. One method of addressing this issue is generating devices that elute antiproliferative drugs . However, the local reservoir of drugs is limited, and problems can arise once the drug depot is depleted.…”

“…One method of addressing this issue is generating devices that elute antiproliferative drugs. [30,31] However, the local reservoir of drugs is limited, and problems can arise once the drug depot is depleted. Two strategies that are more promising are the development of materials that exhibit similar mechanical properties to the native vasculature and the development of materials that foster a functioning endothelium.…”

Mechanisms of antiproliferative drug release from bioresorbable porous structures

“…The stent Taxus contains approximately 50–200 μg (1 μg/mm 2 ) paclitaxel, where ∼2 μg are released within 15 days and 92.5% remain in the matrix for a long time 12. Controlled release of antiproliferative drugs from various polymeric systems for stent applications and local cancer treatment is well described in a review article that has just been published 19. It is clear from these studies that since antiproliferative agents are water insoluble, high surface area devices should be developed in order to obtain their release in a desired manner.…”