Mechanisms of action of novel skin penetration enhancers: phospholipid versus skin lipid liposomes.
Employing thermal analysis, we investigated the mechanism of action of novel enhancers and probed phospholipid (PL) versus stratum corneum lipid (SCL) liposomes as model membranes. The enhancers included octyl salicylate (OS), padimate O (PADO) and 2-(1-nonyl)-1,3-dioxolane (ND). The negative controls were the empty liposomes. Positive controls employed dimethylsulfoxide (DMSO) and Azone (AZ). For PL liposomes, DMSO sharpened the transitions. AZ abolished the pre-transition, broadened the main transition and linearly reduced its transition temperature (T(m)). OS or PADO reduced T(m) and size of pre-transition, broadened the main transition and decreased its T(m) (non-linearly). ND abolished the pre-transition but increased T(m) of the main endotherm, suggesting retardation rather than enhancement. The results of SCL correlated with PL liposomes except for ND. In SCL liposomes, ND reduced T(m) and broadened the peaks indicating lipid disruption, which indicated its enhancing effects. In conclusion, OS, PADO and ND can enhance drugs by disrupting intercellular lipid domain but they differ from AZ in terms of the relationship between efficacy and concentration. Although PL liposomes are simple model membranes with sharp transitions which give detailed information about the effects of enhancers, they can provide misleading results. Simultaneous use of other models like SCL liposomes is recommended.
El Maghraby
Gamal M M
GM
The School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Lower Ground Floor, Building 504, Corner Boyle Crescent and Glasgow Terrace, Grafton, Private Bag 92019, Auckland, New Zealand. gmmelmag@yahoo.com
Campbell
Michael
M
Finnin
Barrie C
BC
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D002518:Ceramides / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D004148:Dioxolanes / Q000494:pharmacology; D008081:Liposomes / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D012459:Salicylates / Q000494:pharmacology; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology*; D044366:Transition Temperature / Q000187:drug effects; D062366:para-Aminobenzoates
D002518:Ceramides; D004148:Dioxolanes; D008081:Liposomes; D008563:Membrane Lipids; D010743:Phospholipids; D012459:Salicylates; D013501:Surface-Active Agents; D062366:para-Aminobenzoates; C111109:2-n-nonyl-1,3-dioxolane; D002784:Cholesterol; D010129:4-Aminobenzoic Acid; C041981:padimate-O