title: Enhancement of Skin Penetration of Hydrophilic and Lipophilic Compounds by pH-sensitive Liposomes.
abstract: OBJECTIVE
  Enhance skin penetration of hydrophilic and lipophilic compounds using liposomes that are responsible to the pH of the skin surface.
  
  
  METHODS
  pH-sensitive liposomes were prepared by a thin layer and freeze-thaw method with dioleoyl phosphatidyl ethanolamine and cholesteryl hemisuccinate. Liposomal fusion with stratum corneum lipid liposomes was measured using fluorescence resonance energy transfer. Particle diameter and zeta potential of the liposomes after fusion were measured by dynamic light scattering and electrophoresis.
  
  
  RESULTS
  Under neutral pH conditions, the diameter of the pH-sensitive liposomes was 130 nm and their zeta potential was -70 mV. In weakly acidic conditions, the diameter was larger than 3,000 nm and the zeta potential was -50 mV. In contrast, the particle diameter and the zeta potential of the non-pH-sensitive liposomes remained constant under various pH conditions. A skin penetration study was performed on hairless mice skin using vertical diffusion cells, showing that the fusion ability of pH-sensitive liposomes was higher than that of non-pH-sensitive liposomes. In the skin penetration study was carried out using hydrophilic (calcein) and lipophilic (N-(7-nitrobenz- 2-oxa-1,3-diazol-4yl)-PE) (NBD-PE) model compounds which were applied to the skin with pH-sensitive liposomes as carrier. The fluorescent compounds contained within the pH-sensitive liposomes permeated the skin more effectively than those within non-pH-sensitive liposomes, and this ability was further enhanced with the lipophilic compound.
  
  
  CONCLUSIONS
  These studies suggest that pH-sensitive liposomes have potential as an important tool for delivery of compounds into the skin.
authors.affiliation: Laboratory of Dermatological Physiology, Faculty of Pharmaceutical Sciences, Josai University.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tokudome
authors.forename: Kaoru
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yurina
authors.initials: Y
authors.lastname: Itaya
authors.forename: Fumie
authors.initials: F
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D051379:Mice; D008812:Mice, Hairless; D009924:Organ Culture Techniques; D010316:Particle Size; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology*
chemical_list: D008055:Lipids; D008081:Liposomes