In Vivo and Ex Vivo Evaluation of a Novel Method for Topical Delivery of Macromolecules Through the Stratum Corneum for Cosmetic Applications

BACKGROUNDEffective topical delivery of large/charged molecules into skin has always been challenging. Chemical penetration enhancers, organic substances that increase permeability of skin, have been in use for decades with variable success. One application of enhancers involves multilamellar vesicles composed of submicron emulsion droplets and micelles surrounded by concentric phospholipid bilayers.OBJECTIVEThis report introduces the next generation of multilamellar vesicles, termed Tiered-Release Vesicles (TRVs), as a new platform for topical delivery of macromolecules such as peptides and hyaluronic acid (HA).METHODSFluorescently labeled peptides and HA, diffusion cells, and confocal microscopy were employed to assess the penetration efficiency of macromolecules in TRV formulations using an ex vivo human skin model. Two in vivo studies utilized punch biopsies followed by histochemical staining and analysis.RESULTSBased on fluorescent intensity, TRV formulations delivered a large peptide more completely (2-5 fold) into ex vivo human skin than optimized liposomes. The penetration of 2 HA species in TRV formulations was 3- to 13-fold higher than with a simple gel vehicle. In the case studies, reduction of solar elastosis was observed from a topical TRV formulation.CONCLUSIONTopical delivery of large peptides and HA into human skin using TRV technology has been demonstrated.