title: The in vitro transport of pergolide from surfactant-based elastic vesicles through human skin: a suggested mechanism of action.
abstract: This paper reports the in vitro transport of pergolide from L-595-PEG-8-L elastic vesicle formulations. Several aspects of vesicular delivery were studied in order to elucidate the possible mechanisms of action and to establish the optimal conditions and drug candidates for usage with L-595-PEG-8-L elastic vesicles. All studies were performed using human skin and flow-through Franz diffusion cells. Pergolide was chosen as model drug. The findings show that there was a strong correlation between the drug incorporation to saturated levels and the drug transport, both of which were influenced by the pH of the drug-vesicular system. The optimal pH was found to be 5.0, giving the highest drug incorporation as well as the highest drug transport. Non-occlusive co-treatment with elastic vesicles improved the skin delivery of pergolide compared to the non-occlusive buffer control by more than 2-fold. However, non-occlusive pre-treatment of skin with empty vesicles did not enhance drug transport. Occlusion improved drug transport from both elastic vesicle as well as buffer solutions due to the fact that water is an excellent penetration enhancer for pergolide. However, in contrast to non-occlusive application, the action of the elastic vesicles themselves was diminished, as occlusive treatments with elastic vesicles showed a lower flux compared to occlusive treatment with the buffer control. Hence, the highest pergolide skin permeation in this study was obtained from an occluded saturated buffer solution, giving a steady-state flux of 137.9 ng/h cm(-2). The volume of application did not have any effect on the drug transport. In conclusion, these results showed no evidence that a penetration enhancing effect is the main mechanism of action. The pH of the drug-vesicular system is an important factor to consider when optimising elastic vesicle delivery systems. Occlusion reduces the actions of elastic vesicles, but could increase the pergolide transport since water is a good penetration enhancer for this particular drug. Based on the results obtained, a mechanism of action for the elastic vesicles was proposed.
authors.affiliation: Department of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, University of Leiden, P O Box 9502, 2300 RA, Leiden, The Netherlands.
authors.forename: P Loan
authors.initials: PL
authors.lastname: Honeywell-Nguyen
authors.forename: Joke A
authors.initials: JA
authors.lastname: Bouwstra
mesh_terms: D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D015194:Diffusion Chambers, Culture; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D004548:Elasticity; D006801:Humans; D010479:Pergolide / Q000737:chemistry / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism*; D013501:Surface-Active Agents / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D004337:Drug Carriers; D013501:Surface-Active Agents; D010479:Pergolide