Publications

Transdermal Curcumin Gel (VAS-101 Drug Candidate) Improves the Microcirculation and Tissue Oxygenation in a Rat Model of Sickle Cell Vaso-Occlusive Episode

Abstract

Objectives Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive episodes (VOEs) that produce microvascular obstruction, tissue hypoxia, and ischemic injury. As the vasculature is increasingly recognized as important in the pathology of SCD, the anti-inflammatory and endothelial-protective properties of curcuminoids have therapeutic potential. VAS-101, a novel transdermal curcuminoid drug candidate designed to overcome poor oral bioavailability of curcumin, was evaluated for its prophylactic effects in an acute rat model of SCD. Methods Sixteen male Sprague Dawley rats were anesthetized and surgically prepared to monitor cardiovascular parameters, blood chemistry, and microvascular interstitial oxygenation (PISFO2). Animals were subjected to exchange transfusion (ET) with isolated human HbSS RBCs and monitored for 2 hours. Results HbSS RBCs produced progressive tissue hypoxia and arteriolar constriction in Sham, while pre-treatment with VAS-101 preserved microvascular oxygenation and arteriolar diameter. VAS-101 animals had attenuated declines in mean arterial pressure after ET, consistent with expected vascular effects of curcumin. Improvements in perfusion and oxygenation were maintained over the 2-hour observation period. Conclusion These findings support the utilization of a transdermal curcuminoid formulation as a potential prophylactic approach to reduce hypoxia, vascular dysfunction, and the risk of VOE in SCD. Further studies in chronic SCD models are warranted to assess pharmacokinetics, long-term efficacy, and whether VAS-101’s prophylactic benefit extends into established VOEs.