Tethering of Chemotherapeutic Drug/Imaging Agent to Bile Acid-Phospholipid Increases the Efficacy and Bioavailability with Reduced Hepatotoxicity

Bioconjugate Chemistry
Vedagopuram SreekanthAvinash Bajaj

Abstract

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 to their poor absorption in the gastrointestinal tract (GIT). Therefore, we designed a gastric pH stable bile acid derived amphiphile where Tamoxifen (as a model anticancer drug) is conjugated to lithocholic acid derived phospholipid (LCA-Tam-PC). In vitro studies suggested the selective nature of LCA-Tam-PC for cancer cells over normal cells as compared to the parent drug. Fluorescent labeled version of the conjugate (LCA-Tam-NBD-PC) displayed an increased intracellular uptake compared to Tamoxifen. We then investigated the antitumor potential, toxicity, and median survival in 4T1 tumor bearing BALB/c mice upon LCA-Tam-PC treatment. Our studies confirmed a significant reduction in the tumor volume, tumor weight, and reduced hepatotoxicity with a significant increase in median survival on LCA-Tam-PC treatment as compared to the parent drug. Pharmacokinetic and biodistribution studies using LCA-Tam-NBD-PC witnessed the enhanced gut absorption, blood circulation, and tumor site accumulation of phosp...Continue Reading

References

Jan 1, 1983·Annual Review of Physiology·M C CareyC M Bliss
Aug 4, 1984·British Medical Journal·A M BlackburnR D Rubens
Mar 4, 2003·Nature Reviews. Drug Discovery·V Craig Jordan
Sep 8, 2007·Journal of Pharmaceutical Sciences·Robert G StrickleyTerrence C Dahl
Dec 11, 2007·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·V Craig Jordan
Jan 4, 2008·Molecular Pharmaceutics·Jean-Bosco TagneRobert J Nicolosi
Mar 22, 2008·Organic & Biomolecular Chemistry· Nonappa, Uday Maitra
May 1, 2009·Journal of Medicinal Chemistry·Palle J PedersenMads H Clausen
Sep 9, 2010·Molecular Pharmaceutics·Twan LammersGert Storm
Sep 17, 2011·Accounts of Chemical Research·Jesse V Jokerst, Sanjiv S Gambhir
Jun 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Poulomi SenguptaShiladitya Sengupta
Jan 31, 2013·Future Medicinal Chemistry·Paul R Ortiz de Montellano
Mar 29, 2013·International Journal of Pharmaceutics·Harshad SheteVandana Patravale
Oct 2, 2013·The Journal of Physical Chemistry. B·Vedagopuram Sreekanth, Avinash Bajaj
Jul 6, 2014·International Journal of Pharmaceutics·Sunil Kumar JenaSarasija Suresh
Jul 17, 2014·The Journal of Physical Chemistry. B·Priyanshu BhargavaAvinash Bajaj
May 21, 2015·Biophysical Journal·Nawal K KhadkaJianjun Pan
May 27, 2015·Chemical Reviews·Bhushan S PattniVladimir P Torchilin
Apr 23, 2016·Expert Opinion on Drug Delivery·Célia FaustinoCatarina Pinto Reis
Dec 19, 2016·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·R Michael DutescuNorbert Schrage
Jan 13, 2017·Molecular Pharmaceutics·Danielle IrbyFeng Li
Apr 2, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dane R Liston, Myrtle Davis

❮ Previous
Next ❯

Citations

Nov 24, 2018·Frontiers in Pharmacology·Nebojša PavlovićMomir Mikov
Sep 9, 2019·ACS Biomaterials Science & Engineering·Vedagopuram Sreekanth, Avinash Bajaj
Dec 11, 2017·ACS Biomaterials Science & Engineering·Prabhu S YavvariAvinash Bajaj

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.