An integrated pharmacokinetic and imaging evaluation of vehicle effects on solute human epidermal flux and, retention characteristics.
OBJECTIVE
Our understanding of the differential effects of topically applied vehicles on solute partitioning and diffusion within the skin is presently limited. In this work, in vitro epidermal partitioning, penetration and multiphoton laser scanning microscopy (MPLSM) imaging studies were used to assess the distribution of 2-naphthol across human epidermis.


METHODS
Four commonly used liquid vehicles (100% water, 20% propylene glycol (PG)/water, 50% ethanol (EtOH)/water and 100% isopropyl myristate (IPM)) were used.


CONCLUSIONS
The maximum flux and membrane retention of 2-naphthol from 50% EtOH/water was almost an order of magnitude or larger than from the other vehicles evaluated whereas IPM resulted in the highest membrane retention and lowest membrane penetration for 2-naphthol than other vehicles. MPLSM studies showed that 2-naphthol solute partitioned favourably into the intercellular lipids and that there was a vehicle-dependent uptake of 2-naphthol into corneocytes.


CONCLUSIONS
The integrated evaluation using in vitro penetration, epidermal retention and MPLSM imaging has shown that vehicle effects on skin penetration occurs by an alteration in the distribution of solutes between the corneocytes and intercellular lipids in addition to the well known mechanisms of altered partitioning into the stratum corneum and enhanced epidermal diffusion.
Winckle
G
G
Therapeutics Research Unit, Southern Clinical School, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Anissimov
Y G
YG
Cross
S E
SE
Wise
G
G
Roberts
M S
MS
D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003627:Data Interpretation, Statistical; D004058:Diffusion; D004817:Epidermis / Q000378:metabolism*; D000431:Ethanol; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D007700:Kinetics; D008081:Liposomes; D008566:Membranes / Q000737:chemistry / Q000378:metabolism; D018613:Microscopy, Confocal; D008875:Middle Aged; D009226:Myristates; D009284:Naphthols / Q000008:administration & dosage / Q000493:pharmacokinetics; D010539:Permeability; D014677:Pharmaceutical Vehicles; D010599:Pharmacokinetics; D019946:Propylene Glycol; D012869:Skin Absorption; D014867:Water
D008081:Liposomes; D009226:Myristates; D009284:Naphthols; D014677:Pharmaceutical Vehicles; D014867:Water; C008205:isopropyl myristate; D000431:Ethanol; D019946:Propylene Glycol; C028405:2-naphthol