Research

Life Sciences & Biotechnology

Title :

Design, synthesis and evaluation of novel hydrophilic conjugates of Cholecalciferol with enhanced bioavailability

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Subhash chander, Amity University, Noida, Uttar pradesh

Timeline Start Year :

2022

Timeline End Year :

2024

Contact info :

Equipments :

Details

Executive Summary :

Vitamin D deficiency is prevalent worldwide, with 80% to 90% reported among all age groups. It is linked to various diseases, including cancer, cardiovascular diseases, autoimmune diseases, and susceptibility to infectious diseases. Despite oral intake of supplemental Vitamin D, the desirable level has not been achieved due to high interpersonal variability in bioavailability due to its low aqueous solubility and stability issues. A proposal has been proposed to design novel hydrophilic ester-based conjugates of Cholecalciferol (VitD3) with selective amino acids, modified dipeptide, and succinic acid to enhance their water solubility. These conjugates are intended to be passively diffused across the brush-border membrane of enterocytes and release vitamin D3 inside the liver through hydrolysis mediated by hepatocyte carboxylesterase enzymes. Amino acids conjugated prodrugs form have been explored in bioavailability enhancement of other poorly water-soluble drugs, but none have been explored for VitD3 bioavailability enhancement. In-silico studies showed enhanced solubility and percentage oral absorption compared to the native form of VitD3. Synthesized compounds will be purified and structure elucidated using spectral techniques. Stability studies will be performed in Simulated Gastric Fluid and Simulated Intestinal Fluid to ensure the compounds are stable in the gastrointestinal condition. The study will contribute to existing knowledge of prodrug strategies, particularly for highly lipophilic compounds with amino acids, including their designing, absorption, cellular uptake, and activation.

Total Budget (INR):

28,46,840

Patents :

1

Organizations involved