Vascular Endothelial Growth Factor-Delivery Systems for Cardiac Repair: An Overview

Abstract

Since the discovery of the Vascular Endothelial Growth Factor (VEGF) and its leading role in the angiogenic process, this has been seen as a promising molecule for promoting neovascularization in the infarcted heart. However, even though several clinical trials were initiated, no therapeutic effects were observed, due in part to the short half life of this factor when administered directly to the tissue. In this context, drug delivery systems appear to offer a promising strategy to overcome limitations in clinical trials of VEGF. The aim of this paper is to review the principal drug delivery systems that have been developed to administer VEGF in cardiovascular disease. Studies published in the last 5 years are reviewed and the main features of these systems are explained. The tissue engineering concept is introduced as a therapeutic alternative that holds promise for the near future.

Inhibition of intimal hyperplasia via local delivery of vascular endothelial growth factor cDNA nanoparticles in a rabbit model of restenosis induced by abdominal aorta balloon injury

“…This issue is important since previous studies investigating the use of VEGF for the treatment of restenosis have produced conflicting results (6)(7)(8)(9)(10)(11)(12)(13)(14). In general, the results indicate that when high cholesterol is involved in model establishment, the beneficial effects of VEGF are mitigated (7,12); however, a number of studies using liposome-and virus-mediated VEGF transfer to injured arteries in a variety of animal models have demonstrated similar beneficial results (13,15).…”

“…As previously discussed, the efficacy of adenovirus-and liposome-mediated VEGF transfer is lower compared with the efficacy achieved using VEGF-containing PLGA nanoparticles. Therefore, future clinical trials using VEGF nanoparticles in humans may result in a higher efficacy (8,23,24).…”

“…The majority of animal studies indicate that local delivery of the VEGF gene is able to promote vascular reendothelialization and prevent restenosis (6)(7)(8), although this remains controversial. Asahara et al demonstrated that VEGF protein stimulated vascular reendothelialization after local delivery into rat carotid arteries following balloon injury (9).…”

“…The authors used immunofluorescence to show that nanoparticles were present in each of the arteries' three layers at 3 h and 24 h post-treatment, and were present in the adventitial layer from days three to seven (27). Furthermore, the arterial vasa vasorum provided a path for nanoparticles to reach the adventitial layer (8). The adventitial layer has been hypothesized to function as a storage pool for nanoparticles, facilitating their release.…”

Surface functionalization of poly(ε-caprolactone) and poly(3-hydroxybutyrate) with VEGF

“…Among them, vascular endothelial growth factor (VEGF) is one of the most used biomolecules. Administered soluble VEGF is rapidly diluted and degrades fast in the human body [7]. However, possible side effects, such as provoking potential malignant growth, are caused by the systemic administration of too much VEGF [1].…”