Quantitative assessment of the transport of elastic and rigid vesicle components and a model drug from these vesicle formulations into human skin in vivo.
The aim of this study was to quantitatively assess the distribution profiles of elastic and rigid vesicle material in human skin in vivo. Furthermore, the distribution profiles of the model drug ketorolac applied in these vesicle formulations was investigated. A deuterium-labelled phospholipid was incorporated into these vesicles to serve as a marker for the vesicle material. The vesicles were loaded with ketorolac at saturated concentrations. Vesicle solutions were applied non-occlusively onto the skin and the treated site was sequentially tape-stripped. Tape-strips were analyzed for vesicle material using attenuated total reflectance-Fourier transform infrared spectroscopy and for ketorolac by extraction of the tape-strips followed by high pressure liquid chromatography. Distribution profiles in the stratum corneum (SC) were obtained for the elastic and rigid vesicle material and for the ketorolac. These profiles have suggested that elastic vesicle material can rapidly enter the deeper layers of the SC and can reach almost the SC-viable epidermal junction. Rigid vesicle material, however, did not penetrate deep into the SC. Furthermore, the elastic vesicles were better than the rigid vesicles in the enhancement of ketorolac transport into human SC. The distribution profile of ketorolac in the deeper SC layers was, however, different from that of the vesicle material. This suggests that once the elastic vesicles partition into the SC, the ketorolac is released from the vesicles. The elastic vesicles are superior to the rigid vesicles both in terms of vesicular transport into the SC and in terms of therapeutic potential as a skin delivery vehicle.
Department of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, University of Leiden, Leiden, The Netherlands.
P Loan
PL
Honeywell-Nguyen
Gert S
GS
Gooris
Joke A
JA
Bouwstra
D000279:Administration, Cutaneous; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001692:Biological Transport; D003903:Deuterium / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004548:Elasticity; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D006801:Humans; D020910:Ketorolac / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D010743:Phospholipids / Q000493:pharmacokinetics; D014867:Water / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010743:Phospholipids; D014867:Water; D003903:Deuterium; D020910:Ketorolac