ABSTRACT
Introduction ...................................................................................................................................... 95 Definition, Structure, and the Main Properties of Ethosomes ........................................................ 96 Mechanism of Skin Permeation Enhancement by Means of Ethosomes ....................................... 97 Various Aspects of Ethosomal Delivery System .............................................................................. 99
Efficiency to Enhance Drug Permeation into and through the Skin .......................................... 99 Skin Permeation Performance of Ethosomes versus Liposomes and
Hydroethanolic Solution...................................................................................................... 99 Enhanced In Vitro Delivery of Molecules with Diverse Chemical Properties ..................... 100 Proof of Concept in Animals and in Clinical Trials ............................................................... 102
Safety Evaluation In Vitro, in Animals and in Human Studies ................................................. 104 Stability and Manufacture........................................................................................................... 104
Summary ......................................................................................................................................... 105 Acknowledgment ........................................................................................................................... 106 References....................................................................................................................................... 106
Liposomes were the first vesicular carrier studied for the delivery of drugs into the skin. Since the early works of Mezei using liposomes for topical drug delivery [1-2], numerous studies have shown that classic liposomes are able to increase drug accumulation in the upper layer of the skin, the stratum corneum (SC) [1-7]. Drug delivery from liposomes is characterized by the formation of a drug reservoir in SC and by lack of penetration into the deeper layers of the skin. Studies by Mezei and Gulusekharam [1, 2] demonstrated that application of triamcinolone acetonide encapsulated within liposomes to depilated rabbit skin in vivo resulted in a fourfold increase in the amount of drug accumulated in
epidermis, as compared to application of the same drug concentration in an ointment base. Touitou et al. [3] found that the application of dyphylline incorporated in unilamellar liposomes caused a high localization of the drug into the skin. In a further study, following the delivery of caffeine from small, unilamellar liposomes, high reservoir of the drug was obtained in the skin [5]. These authors by using quantitative skin autoradiography have examined the distribution of the drug in the various strata of the skin where the greatest concentration was found in the epidermis and the lowest in the dermis. Junginger’s group has shown by scanning and freeze-fracture electron micrographies (SEM and FFEM) that liposomes and nonionic surfactant vesicles, niosomes, adsorb on the surface of SC [6, 7]. It was suggested that for these kinds of vesicles, it appears to be thermodynamically favorable upon application to the skin to aggregate, fuse, and adhere to the SC surface in stacks of lamellar sheets. Moreover, no ultrastructural changes in the deeper layers of SC were reported with conventional liposomal systems tested.
