Sustained local drug delivery from a novel polymeric ring to inhibit intimal hyperplasia

Abstract

The long-term clinical success of autologous vein and synthetic vascular grafts are limited because of the development of anastomotic intimal hyperplasia (IH). We have previously published data suggesting that cyclosporine (CyA) may reduce the development of IH in a canine model (Hirko et al., J Vasc Surg 1993;17:877-887). However, systemic administration of CyA could create serious adverse effects. Therefore, it is our long-term goal to test the hypothesis that the controlled local release of CyA from a polymeric vascular wrap would prevent the development of IH. To test this hypothesis, we developed a controlled release polymeric ring that could be placed around anastomotic sites to deliver therapeutic drugs locally. The ring is a composite polymeric device consisting of poly(DL-lactide-co-glycolide) (PLGA) microspheres embedded in a poly(ethylene glycol) hydrogel. Several in vitro studies were conducted to evaluate the effects of different sterilization procedures on the properties of the device. It was determined that gamma sterilization was the preferred sterilization method of choice for this device. In vivo studies were conducted on a swine model to evaluate the biocompatibility of the ring. The histological findings of the ring implants at 2 and 4 weeks demonstrate the biocompatibility of this device.

Vein graft failure

“…Indeed a number of experimental programs have exploited adventitial delivery of therapeutic agents to the vein graft to take advantage of these mechanisms. [75-78]…”

Unidirectional and sustained delivery of the proresolving lipid mediator resolvin D1 from a biodegradable thin film device

“…Previous attempts at perivascular drug delivery from polymer devices have included particles, wraps, cuffs and hybrid assemblies of PLGA, PCL, or both polymers. These attempts have aimed to regulate inflammation and proliferation with various drugs, such as rapamycin, 18,19 paclitaxel, 18,20,21 cyclosporine A, 22 and sunitinib. 23 However, clinical use of these drugs has been limited due to cytotoxicity, which merits the development of a drug delivery approach focused on SPM (e.g., RvD1).…”

Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model

“…Despite several theoretical advantages [ 11 , 12 , 13 , 14 , 15 ], a perivascular drug delivery device should resolve several challenges in terms of inflammatory change to the treated tissue after degradation, the influence of vascular constriction, controlled drug release, ease of application, or drug localization. In our previous study [ 22 ], a highly flexible and porous silk fibroin MN wrap was shown to enhance cell compatibility and maintain the biological and structural unity of vascular tissue with minimal deformation.…”

“…In recent studies, different forms of external vascular devices such as films, wraps, depot gels, meshes, rings, or microparticles/nanoparticles were reported for perivascular delivery of an antiproliferation drug such as paclitaxel or sirolimus to prevent neointimal hyperplasia [ 11 , 12 , 13 , 14 , 15 ]. In our previous studies, an external applicable perivascular microneedle (MN) device with paclitaxel and sirolimus showed appropriate drug distribution in vascular tissue and significantly decreased neointimal hyperplasia of the abdominal aorta in a rabbit balloon injury model [ 16 , 17 ].…”