Drug Discovery Today  Volume 17, Numbers 21/22  November 2012 REVIEWS Ultra-adaptable nanovesicular systems: a carrier for systemic delivery of therapeutic agents Ajay Kumar, Kamla Pathak and Vikas Bali Department of Pharmaceutics, Rajiv Academy for Pharmacy, Mathura 281001, Uttar Pradesh, India The skin acts as a barrier and prevents transcutaneous delivery of therapeutic agents. Transferosomes are novel vesicular systems that are several times more elastic than other vesicular systems. These are composed of phospholipids, edge activator and ethanol and are applied in a non-occlusive manner. Owing to their ultradeformability, they have the potential to deliver therapeutic agents across the intact skin in a non-invasive and non-allergenic manner. The present review attempts to provide an in-depth account of ultra-adaptable nanovesicular systems. The current investigation, besides compiling existing knowledge in a systematic manner, also includes information like regulatory aspects of excipients used in preparation, summary of clinical investigations performed, marketed preparations available, research reports and patent reports related to transfersomes. The delivery of therapeutic agents transdermally has received considerable interest because of the safety and convenience of drug administration via this route. In addition, the transdermal route has numerous advantages compared with conventional approaches to the administration of therapeutic agents, including circumvention of hepatic first pass metabolism, predictable and extended duration of activity, a reduction in adverse effects [1,2], improvement of physiological as well as pharmacological responses, avoidance of gastric disturbances and fluctuations in drug levels, avoidance of inter- and intra-patient variations in drug absorption [3] and, finally, improvement in patient compliance [4]. The major issue surrounding the transdermal route is the anatomical organization of skin, which enables it to behave as a barrier, controlling the loss of water, electrolytes and other con- stituents, and preventing the entry of therapeutic as well as deleterious agents from the outer milieu. The uppermost stratum of the skin is the stratum corneum, which comprises cells loaded with keratin, called corneocytes, implanted in a lipid matrix and arranged in a multilayered structure. It is very thin (approximately 1–10% of total skin thickness) and is responsible for over 80% of the total resistance of the skin to the transport of substances [1]. Various approaches, including vesicular systems, have been used to alter skin to allow the transport of therapeutic agents across it. Vesicles as transporters of therapeutic agents across the skin Vesicles are colloidal structures that have an aqueous core sur- rounded by a bilayer comprising amphiphilic molecules (e.g. phos- pholipids or non-ionic surfactants). An excess of water leads to the formation of one or more concentric bilayers known as unilamellar or multilamellar vesicles [5]. Colloidal systems are unable to pass through the skin because of its compact structure. However, the mixed lipid vesicle-based nanocarriers (i.e. highly adaptable col- loids) are able to pass through narrow pathways between skin cells to mediate drug transport [6–8]. The aqueous core of these vesicles is capable of loading hydrophilic drugs, whereas amphiphilic, hydro- phobic and charged hydrophilic drugs can be linked with the vesicle bilayer through hydrophobic and/or electrostatic interactions [9]. These vesicles can act as penetration enhancers to transport loaded therapeutic agents into or across the biological membranes, and as a rate-controlling factor for the alteration of absorption into the systemic circulation [2]. Encapsulation of therapeutic agents by vesicular structures is expected to prolong the duration of action of the drugs in the systemic circulation and to also reduce their toxicity by facilitating selective uptake of the drug through vesicular systems [10]. Vesicular systems used for topical application of bioactives include transfersomes, liposomes, niosomes and etho- somes [11]. Ethosomes considered to be adaptable vesicles have been investigated in our laboratory for the efficacious topical Reviews  POST SCREEN Corresponding author:. Bali, V. (vksbali@gmail.com) 1359-6446/06/$ - see front matter ß 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.drudis.2012.06.013 www.drugdiscoverytoday.com 1233