Combination of Nanocurcumin and Arginine Incorporated Injectable Chitosan Hydrogel for the Maintenance of Vascular Perfusion in Ischemia

Abstract

Ischemic injury occurs due to the reduction of blood supply to affected tissues, secondary to narrowing of blood vessels. One of the main causes for ischemia is atherosclerosis. The disease can manifest either in the acute or chronic form. Peripheral limb ischemia, a chronic ischemic disease, is highly prevalent in both developed and developing countries. Patients suffering from this type of ischemic condition develop sustained limb pain which progresses to limb necrosis that may require amputation. Several therapeutic strategies aim at decreasing the harmful effects of limb ischemia. Enhancement of angiogenesis in the ischemic limb is a promising strategy that has been in focus in the recent past. Studies have demonstrated that measures to sustain or increase vasculature in ischemic limbs lead to better tissue oxygenation and tissue viability. Therapeutic angiogenesis often involves delivering growth factors or cells to re-vascularize tissues. However, clinical trials adopting this strategy have failed to show benefit, primarily because of barriers posed by endothelial dysfunction. Arteriogenesis is another mechanism that involves the modelling of existing arterial network and increases blood perfusion, primarily via the nitric oxide pathway in vascular endothelial cells. However, as observed in angiogenesis, endothelial dysfunction appears to play a detrimental role in arteriogensis as well. In this study we have tested a novel strategy to prevent ischemia associated endothelial dysfunction and to enhance tissue perfusion by administration of an injectable hydrogel system containing nanocurcumin complex and L-arginine.Methods: Nanocurcumin complexes were prepared by ionic gelation method and incorporated into chitosan hydrogel along with L-arginine (nC/R/Ch). SEM, FTIR and rheological analysis were performed to characterize the nC/R/Ch. Antioxidant activity of nC/R/Ch was assessed using the DPPH assay. Picrogreen assay and tube formation assay were performed to determine (HUVECs)cell toxicity and angiogenic..