Preclinical Implication of liposomal hydrogel loaded dual drug Metadoxine and PDE-5 Inhibitor for transdermal delivery to target myofibroblast to ameliorate fibrosis
Implementing Organization
Principal Investigator
Prof. Vikas Agarwal
sanjay Gandhi Postgraduate Institute Of Medical sciences, Uttar Pradesh
CO-Principal Investigator
Dr. satyakam Patnaik
Csir Indian Institute Of Toxicology Research, Lucknow, Uttar Pradesh
CO-Principal Investigator
Dr. Durga Prasanna Misra
sanjay Gandhi Postgraduate Institute Of Medical sciences, Lucknow, Uttar Pradesh-226014
About
Fibrosis is a condition caused by chronic inflammation, vasculopathy, and excessive extracellular matrix deposition in the skin and internal organs. There is currently no available treatment for fibrosis, with TGF-β1 activation being the hallmark of fibrotic pathogenesis. serotonin (5-HT) released from platelets has been implicated in fibrosis in carcinoid tumors and animal models of skin fibrosis. The phosphodiesterase-5 inhibitor has been reported to control fibrosis by activating cGMP-mediated protein kinase G activation, inhibiting canonical and non-canonical signaling pathways. The study aims to synthesize a transdermally deliverable dual drug, Tadalafil and Metadoxine, targeting myofibroblast receptor AV-Integrin through surface modification of RGD through liposomal hydrogel. The drug will be synthesized using a thin-film hydration method and incorporated in hydrogel for transdermal delivery. The anti-fibrotic efficacy of the transdermal drug will be evaluated on the HADF cell line and dermal scleroderma induced sKH-1 mouse model. Topical administration is expected to be an appealing alternative to oral routes, suppressing toxicity and reducing dose concentration.