title: Decrease of liposomal size and retarding effect on fluconazole skin permeation by lysine derivatives.
abstract: Liposomes are ideal dermal drug delivery systems because of their ability to alter the biodistribution profile of incorporated drugs. In a novel approach to optimize the liposomal microstructure, lysine derivatives were employed. The effect of the oligopeptides Lys-5 and Lys-7 on the structure as well as on the skin permeation of the antimycotic drug fluconazole in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine vesicles was studied using a variety of techniques. It was demonstrated by addition of the shift reagent praseodymium(III)chloride and subsequent (31)P NMR measurements that the liposomes produced consisted mainly of unilamellar vesicles. This was confirmed by cryo-transmission electron microscopy. The addition of Lys-5 and Lys-7 induced a structural change resulting in a decrease in particle size between 10% and 40% and a retarding effect on fluconazole skin permeation.
authors.affiliation: Research Platform Characterisation of Drug Delivery Systems on Skin and Investigation of Involved Mechanisms, University of Vienna, Vienna, Austria.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Schwarz
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Kählig
authors.forename: Nadejda B
authors.initials: NB
authors.lastname: Matsko
authors.forename: Martin
authors.initials: M
authors.lastname: Kratzel
authors.forename: Markus
authors.initials: M
authors.lastname: Husa
authors.forename: Claudia
authors.initials: C
authors.lastname: Valenta
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000279:Administration, Cutaneous; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D020285:Cryoelectron Microscopy; D004355:Drug Stability; D015725:Fluconazole / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D010539:Permeability; D011221:Praseodymium / Q000737:chemistry; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine; D013678:Technology, Pharmaceutical / Q000379:methods; D053835:Unilamellar Liposomes
chemical_list: D000935:Antifungal Agents; D009842:Oligopeptides; D053835:Unilamellar Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D015725:Fluconazole; D008239:Lysine; D011221:Praseodymium