Tethering of Chemotherapeutic Drug/Imaging Agent to Bile Acid-Phospholipid Increases the Efficacy and Bioavailability with Reduced Hepatotoxicity
作者： Vedagopuram Sreekanth , Nihal Medatwal , Sandeep Kumar , Sanjay Pal , Malyla Vamshikrishna
DOI: 10.1021/ACS.BIOCONJCHEM.7B00564
关键词: Chemistry 、 Pharmacology 、 Bile acid 、 Drug 、 Phospholipid 、 Toxicity 、 Bioavailability 、 Tamoxifen 、 Cancer cell 、 Lithocholic acid
摘要: Weakly basic drugs display poor solubility and tend to precipitate in the stomach’s acidic environment causing reduced oral bioavailability. Tracing of these orally delivered therapeutic agents using molecular probes is challenged due their absorption gastrointestinal tract (GIT). Therefore, we designed a gastric pH stable bile acid derived amphiphile where Tamoxifen (as model anticancer drug) conjugated lithocholic phospholipid (LCA-Tam-PC). In vitro studies suggested selective nature LCA-Tam-PC for cancer cells over normal as compared parent drug. Fluorescent labeled version conjugate (LCA-Tam-NBD-PC) displayed an increased intracellular uptake Tamoxifen. We then investigated antitumor potential, toxicity, median survival 4T1 tumor bearing BALB/c mice upon treatment. Our confirmed significant reduction volume, weight, hepatotoxicity with increase medi...
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