The interaction of the penetration enhancer DDAIP with a phospholipid model membrane.
Differential scanning calorimetry (DSC) was used to investigate the mechanism of action of a proprietary skin penetration enhancer, dodecyl-2-(N,N-dimethylamino)propionate (DDAIP) in dipalmitoylphosphatidylcholine (DPPC) liposomes. Furthermore, the effect of enhancer concentration on lipid thermotropic transitions was investigated. With increasing concentrations of DDAIP (from 5 to 50 mol%), the main transition peak shifted to lower temperatures and became more broad. The pretransition peak also shifted to lower temperatures with increasing concentrations of DDAIP and disappeared completely above an enhancer concentration of 20 mol%. Main transition and pretransition enthalpies of reaction decreased with increasing DDAIP concentration, indicating that enhancer treatment destabilized both rippled gel and liquid crystal phases within the bilayer. At and above a DDAIP concentration of 33.3 mol%, an additional transition was evident, indicating the presence of two phases of enhancer-lipid complex. Results suggest that DDAIP enhances drug transport by interacting with the polar region of the phospholipid bilayer and also by increasing the motional freedom of lipid hydrocarbon chains.
Wolka
Anne M
AM
Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Avenue, Lawrence, KS 66047, USA.
Rytting
J H
JH
Reed
B L
BL
Finnin
B C
BC
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D004305:Dose-Response Relationship, Drug; D005782:Gels; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes; D044367:Phase Transition; D013696:Temperature
D005782:Gels; D008051:Lipid Bilayers; D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; C085388:dodecyl 2-(N,N-dimethylamino)propionate; D000409:Alanine