Improved skin oxygenation after benzyl nicotinate application in different carriers as measured by EPR oximetry in vivo.
The development of formulations, which increase skin oxygenation and of methods for measuring oxygen levels in skin are important for dealing with processes affected by the level of oxygen, e.g., rate of healing and efficiency of radiation oncology. In this study we have investigated the role of carriers on the efficacy of benzyl nicotinate (BN) action in skin after dermal application in different formulations by EPR oximetry in vivo. The time course of pO2 in the skin after application of rubefacient is followed directly for the first time. The results obtained proved the applicability of in vivo EPR oximetry as a sensitive method by which small alterations in pO2 can be detected. We have found that the type of vehicle significantly influences the time when BN starts to act, the duration of its action, and the maximal increase in pO2. The ranking of vehicle efficiency was: lipid nanoparticles in hydrophilic gel>liposomes in hydrophilic gel>hydrophilic gel>hydrophobic ointment>hydrophobic cream. Primarily the semi-solid vehicle determines the lag-time of action, but the maximal oxygen level is influenced decisively by the particulate carrier systems. BN effectiveness was dose dependent. 2.5% w/w concentration of BN appears to be the most appropriate for therapeutic application. After repeated application a successive increase of pO2 base line in skin and of the maximal pO2 was noticed.
Krzic
M
M
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, SI-1000 Ljubljana, Slovenia.
Sentjurc
M
M
Kristl
J
J
D000279:Administration, Cutaneous; D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009539:Nicotinic Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010092:Oximetry; D010100:Oxygen / Q000032:analysis / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
D009539:Nicotinic Acids; C025653:nicotinic acid benzyl ester; D010100:Oxygen