Life Sciences & Biotechnology
Title : | Developing Repertoire of Orally Deliverable Phospholipid-Drug Conjugates (PDCs) for Targeting Colorectal and Hepatocellular Carcinoma. |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Avinash Bajaj, Regional Centre For Biotechnology, Faridabad, Haryana |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | bajaj@rcb.res.in |
Details
Executive Summary : | The Indian Council of Medical Research (ICMR) predicts a 12% increase in cancer burden in India by 2025, with gastrointestinal (GI) tract cancers contributing around 20% of the total cancer burden. Oral delivery of anticancer drugs is an ideal treatment strategy for gastrointestinal cancers like colorectal and hepatocellular carcinoma. However, challenges such as poor solubility, instability in the GI tract, and poor bioavailability pose significant challenges. To address these issues, a proposal has been proposed to develop phospholipid-drug conjugates containing phosphocholine conjugated lithocholic acid tethered to gemcitabine, docetaxel, and 5-fluoruracil. These conjugates will enhance the stability of anticancer drugs in the GI tract, increase intestinal permeability, and improve bioavailability. The study will evaluate the stability of these conjugates under various pH and enzyme conditions, simulate gastric and intestinal fluid, and pass through mucosal and epithelial barriers. The anticancer activities of these conjugates will be tested against human and mouse liver and colon cancer cells. Efficacy of the conjugates will be tested in two chemically-induced CRC and HCC models, as well as genetically engineered models. The impact of PDCs on tumor proliferation and cell death will be quantified using flow cytometry and immunohistochemistry. The study will also investigate the effect of PDCs on macrophage polarization in tumor tissues and the effects of immunotherapeutic strategies like anti-PD-L1 antibodies in combination with PDCs. successful execution of this proposal will fill gaps in oral delivery of chemotherapeutics for cancer treatment, overcoming challenges such as low bioavailability, poor efficacy, and resistance to anti-cancer drugs. |
Total Budget (INR): | 67,81,600 |
Organizations involved