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Prodrugs are currently used even in early stages of drug development, and a significant percentage of all drugs in the market are prodrugs. The focus of this article is lipidic prodrugs, a strategy whereby a lipid carrier is covalently bound to the drug moiety. The increased lipophilicity of the lipid\u2010drug conjugate can improve the pharmacokinetic profile and provide meaningful advantages: increased absorption across biological barriers, prolonged circulation half\u2010life, selective distribution profile (eg brain penetration), reduced hepatic first\u2010pass metabolism, and overall enhanced bioavailability of the parent drug. Moreover, lipidic prodrugs may join the endogenous lipid trafficking pathways, thereby facilitate drug targeting, either by selective absorption pathway (eg lymphatic transport) or drug release at specific target site(s). The different lipid\u2010drug conjugates (triglyceride\u2010, fatty acids, phospholipid\u2010, and steroid\u2010based prodrugs), the physiological barriers that challenge the absorption of these conjugates, followed by their current utilization and potential clinical benefits are described and analyzed, and future opportunities this approach could provide are discussed. Altogether, lipidic prodrugs represent an exciting approach for improving different aspects of oral drug delivery\/therapy and may provide solutions for various unmet needs; the use of this strategy is expected to grow.<\/jats:p>","DOI":"10.1002\/med.21533","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T13:34:41Z","timestamp":1539610481000},"page":"579-607","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Lipidic prodrug approach for improved oral drug delivery and therapy"],"prefix":"10.1002","volume":"39","author":[{"given":"Milica","family":"Markovic","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology School of Pharmacy, Faculty of Health Sciences, Ben\u2010Gurion University of the Negev Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimon","family":"Ben\u2010Shabat","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology School of Pharmacy, Faculty of Health Sciences, Ben\u2010Gurion University of the Negev Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahar","family":"Keinan","sequence":"additional","affiliation":[{"name":"Cloud Pharmaceuticals Inc. 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