A review on the treatment of intimal hyperplasia with perivascular medical devices: role of mechanical factors and drug release kinetics.

INTRODUCTION: Intimal hyperplasia (IH) is a significant factor limiting the success of revascularization surgery for blood flow restoration. IH results from a foreign body response and mechanical disparity that involves complex biochemical reactions resulting in graft failure. The available treatment option utilizes either different pharmacological interventions or mechanical support to the vascular grafts with limited success. AREAS COVERED: This review explains the pathophysiology of IH, responsible mechanical and biological factors, and treatment options, emphasizing perivascular devices. They are designed to provide mechanical support and pharmacology actions. The perivascular drug delivery concept has successfully demonstrated efficacy in various animal studies. Accurate projections of drug release mechanisms using mathematical modeling could be used to formulate prolonged drug elution devices. Numerical modeling aspects for the prediction of design outcomes have been given due importance that fulfills the unmet clinical need for better patient care. EXPERT OPINION: IH could be effectively prevented by simultaneous mechanical scaffolding and sustained local drug delivery. Future perivascular medical devices could be designed to integrate these essential features. Numerical modeling for device performance prediction should be utilized in the development of next-generation perivascular devices.

Perivascular patch using biodegradable polymers: Investigation of mechanical and drug elution characteristics.

Intimal hyperplasia (IH) is the primary cause for the vascular graft stenosis. Perivascular devices offer a potential treatment option to reduce the impact of intimal hyperplasia by providing mechanical support and local administration of therapeutic agents to control cellular overgrowth. In the present study, a perivascular patch primarily made up of biodegradable polymer, Poly L-Lactide, has been designed with adequate mechanical strength and ability for sustained drug elution of anti-proliferative drug (Paclitaxel). The elastic modulus of the polymeric film has been optimized by blending the base polymer with different grades of biocompatible polyethylene glycols. Using design of experiments, the optimized parameters were obtained as PLLA with 2.5% PEG-6000 and have shown 3.14 MPa elastic modulus. The film prepared based on optimum conditions has been employed for prolonged drug delivery (about four months) under simulated physiological conditions. The addition of drug release rate enhancer (polyvinyl pyrrolidone K90F) has improved the drug elution rate and ∼83% drug was released over entire study period. The molecular weight of the base biodegradable polymer was estimated by gel permeation chromatography (GPC) which remained unchanged during the drug release study duration. Evidences of Paclitaxel drug crystallization were found to contribute to the sustained drug elution. The SEM examination of the surface morphology post-incubation revealed micropores on the surface, contributing to the overall drug release rate. The study concluded that perivascular biodegradable films could be tailored for their mechanical properties, and sustained drug elution could also be formulated with reasonable choices of biodegradable polymer and biocompatible additives.

Nanoparticle-eluting stents for coronary intervention: formulation, characterization, and in vitro evaluation.

Coronary artery disease (CAD) is currently a leading cause of death worldwide. In the history of percutaneous coronary intervention for the treatment of CAD, a drug-eluting stent (DES) is recognized as a revolutionary technology that has the unique ability to significantly reduce restenosis and provide both mechanical and biological solutions simultaneously to the target lesion. The aim of the research work was to design and fabricate DES coated with a nanoparticulate drug formulation. Sirolimus, an inhibitor of the smooth muscle cell (SMC) proliferation and migration, was encapsulated in polymeric nanoparticles (NPs). The NP formulation was characterized for various physicochemical parameters. Cell viability and cell uptake studies were performed using human coronary artery smooth muscle cells (HCASMCs). The developed NP formulation showed enhanced efficacy compared to plain drug solution and exhibited time-dependent uptake into the HCASMCs. The developed NP formulation was coated on the Flexinnium™ ultra-thin cobalt-chromium alloy coronary stent platform. The NP-coated stents were characterized for morphology and residual solvent analysis. In vitro drug release was also evaluated. Ex vivo arterial permeation was carried out to evaluate the NP uptake from the surface of the stents. The characterization studies together corroborated that the developed NP coated stent can be a promising replacement of the current DESs.

Nanocoatings on implantable medical devices.

The global medical device industry has experienced significant growth over the past 5 years. The surge of patent publications in the field bears testimony to this fact. The advent of nanotechnology has opened up newer unexplored vistas in the field of medical devices. This review summarizes patents employing the principles of nanotechnology in the formulation of coatings for implantable medical devices. Patents selected have at least one entity or structure with dimensions in the nanometer range, which results in a therapeutic value addition. The strategies reviewed pertain to tackling issues such as restenosis and thrombosis in addition to improving the overall acceptability of the implantable medical device, particularly those placed in the vasculature.