Self-assembled ufasomes of unsaturated fatty acids: mechanisms, characterization, and drug delivery potential

Ufasomes-vesicular systems formed from long-chain unsaturated fatty acids such as oleic acid-have re-emerged as cost-effective, biocompatible alternatives to phospholipid liposomes. These bilayered assemblies self-organize at specific pH conditions and efficiently encapsulate both hydrophilic and lipophilic drugs. Their highly fluid membranes, attributed to cis-double-bond-induced structural disorder, enhance interaction with biological barriers, particularly the stratum corneum, making them valuable for topical and transdermal delivery. This review outlines the chemistry and self-assembly of ufasomes, followed by a critical appraisal of preparation techniques-including thin-film hydration and reverse-phase evaporation-and their influence on vesicle size, stability and encapsulation efficiency. Advantages such as biocompatibility, biodegradability and pH-responsive release are highlighted alongside limitations including pH-dependent instability and oxidative susceptibility. Key characterization approaches are summarized, and the therapeutic scope of ufasomes is examined, encompassing enhanced dermal delivery of antifungals and antidepressants, targeted cancer therapy, and improved oral bioavailability of nutraceuticals like oleuropein. The review concludes with emerging strategies to overcome current constraints and perspectives on advancing ufasomes toward clinical translation as versatile drug-delivery systems.