ULTRADEFORMABLE LIPOSOMES FOR TOPIC APPLICATION OF COSMETIC ACTIVES CAN MODULATE THEIR DESTINATION ACROSS THE STRATUM CORNEUM

J MONTANARI, MJ MORILLA, EL ROMERO

Congreso; 26 thCongress of the International Federation of Societies of Cosmetic Chemists; 2010

Introduction: The lipid matrix of ultradeformable liposomes (UDL) have a decreased elastic modulus as compared to conventional liposomes (CL), specially designed to increase the transcutaneous delivery of actives. Unlike CL, UDL are capable of penetrate across the stratum corneum (SC) driven by the transepitelial humidity gradient, instead of aggregate or coalesce on the skin surface. Instead of a conventional sustained release but modifying the transcutaneous pathways, once applied under non-occlusive conditions onto the skin, UDL could be a powerful tool for the controlled/targeted delivery of cosmetic actives. UDL are capable of carrying both hydrophobic and hydrophilic actives loaded in their lipid matrix or in their aqueous interior, respectively. Of the few dozens of nanocosmetic products in the market to date from 2005 on, most of them are based in the occlusive penetration of actives loaded into nanostructured lipid carriers (NLC), and no formulations include UDL, which until now has been tested almost exclusively for the delivery of pharmaceutics. There is little information available –or it is controversial- about the final destiny of both the lipid matrix and its actives upon skin penetration. With the aim of evaluate their capability of enhance penetration of cosmetics, as well as the risk of systemic access of some actives, the in vitro skin penetration of UDL carrying both hydrophilic and hydrophobic fluorescent compounds and Quantum Dots (QD) was tested. Methods: The Saarbrücken Penetration Model was adapted for non-occlusive conditions and different UDL (100 nm diameter) were applied on human skin explants excised from abdominal reductive surgery at 0.12 mg of lipids/cm2. Tested suspensions were the following: UDL containing the fluorescent hydrophilic fluorescent probe HPTS (UDL-HPTS), similar UDL containing the lipophilic probe Rhodamine-PE (UDL-HPTS-Rh), and UDL containing Quantum Dots (UDL-QD) as a model for particulate entrapped material. Similarly labeled CL were used as control. Samples were incubated at 35 °C, and penetration was analyzed by diverse techniques: HPTS quantification after tape stripping and extraction, optical sectioning by confocal laser scanning microscopy (CLSM), transversal cryosectioning and fluoromicrgraphy by CLSM. Results: UDL-HPTS penetrated the SC in an amount almost 7 times higher than CL-HPTS, but no significant differences were observed when incubation time was extended from 1 to 5 hours. Fluoromicrography revealed that CL could not enter the SC (neither to promote the penetration of the fluorescent labels), while UDL allowed to find Rhodamine-PE into the SC up to 14 mm depth, and HPTS in a separate layer reaching the viable epidermis at a mean depth of 24 mm. QD fluorescence from UDL-QD was detected all along the SC, while when applied free, QD were found not only into the SC but also at the viable epidermis. Conclusions: Cutaneous penetration of UDL triggered the release of their acqueous content to be shuttled from the lipid matrix to the viable epidermis, a fact which could be useful for the delivery of cosmetic actives to the epidermis, and whose hydrophilic nature could not allow their penetration through the SC with excipients. Nevertheless, the risk of systemic delivery in this case must be considered depending on the nature of the active. On the other hand, both the lipophilic marker and the QD were confined to all the SC extension. Since the penetration profile of free QD reached the viable epidermis, it could be suggested that the lipid matrices of UDL did not disassemble themselves. Probably the penetration stress could induce disruption of the UDL membranes which could explain the release of the aqueous content. Therefore, UDL could also serve as vehicles for the accumulation of hydrophobic or particulate actives restricted to the SC. It could also be an interesting alternative for the improved penetration of substances whose systemic access under other conditions would imply the risk of accumulation in secondary organs