title: Phospholipid-Based Prodrugs for Drug Targeting in Inflammatory Bowel Disease: Computational Optimization and In-Vitro Correlation.
abstract: In inflammatory bowel disease (IBD) patients, the enzyme phospholipase A2 (PLA2) is overexpressed in the inflamed intestinal tissue, and hence may be exploited as a prodrug-activating enzyme allowing drug targeting to the site(s) of gut inflammation. The purpose of this work was to develop powerful modern computational approaches, to allow optimized a-priori design of phospholipid (PL) based prodrugs for IBD drug targeting. We performed simulations that predict the activation of PL-drug conjugates by PLA2 with both human and bee venom PLA2. The calculated results correlated well with in-vitro experimental data. In conclusion, a-priori drug design using a computational approach complements and extends experimentally derived data, and may improve resource utilization and speed drug development.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. arikd@bgu.ac.il.
authors.forename: Arik
authors.initials: A
authors.lastname: Dahan
authors.forename: Shimon
authors.initials: S
authors.lastname: Ben-Shabat
authors.forename: Noa
authors.initials: N
authors.lastname: Cohen
authors.forename: Shahar
authors.initials: S
authors.lastname: Keinan
authors.forename: Igor
authors.initials: I
authors.lastname: Kurnikov
authors.forename: Aaron
authors.initials: A
authors.lastname: Aponick
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL 32608, USA. ezimmer2@ufl.edu.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Zimmermann
mesh_terms: D016503:Drug Delivery Systems; D006801:Humans; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008958:Models, Molecular; D054467:Phospholipases A2 / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry*; D011355:Prodrugs / Q000627:therapeutic use*
chemical_list: D010743:Phospholipids; D011355:Prodrugs; D054467:Phospholipases A2