Nowadays, prodrugs are no longer used as a last resort, rather, they are intentionally designed at the early stages of drug development. Lipidic prodrug strategy, where a drug moiety is covalently bound to a lipid carrier, was initially proposed half a century ago, yet, this approach still remains to be explored. Lipidic prodrugs can join physiological lipid metabolic pathways, and hence provide drug targeting via lymphatic transport or site-specific drug release, improve drugs' pharmacokinetic profile, overcome obstacles originating from biological barriers and bypass hepatic first-pass metabolism. Physiological pathways of lipid processing, uses of different lipidic prodrugs and their clinical benefits are overviewed. Overall, lipidic prodrugs present a promising approach for overcoming different obstacles and fulfilling various unmet needs in drug delivery/targeting.
Keywords: biopharmaceutics; cholesterol; drug delivery; fatty acid; lipid; lymphatic drug transport; phospholipid; prodrug; triglyceride.