Effect of dimethyl sulfoxide on drug permeation through human skin

Abstract

The effect of the presence of dimethyl sulfoxide (in admixture with water) on the sorption and permeation rate of scopolamine base in human skin in vitro has been measured as a function of drug concentration in aqueous solution. The equilibrium sorption of scopolamine by skin from solution appears to be unaffected by the presence of even high concentrations of dimethyl sulfoxide in the solution phase. In the absence of a transdermal gradient of DMSO (or water), the permeability of skin to scopolamine in the presence of DMSO i.; about twofold higher than in its absence, suggesting that the diffusivity of scopolamine in the stratum corneum is somewhat elevated by the solvating action of DMSO.When, however, a gradient of DMSO concentration is impressed across the skin (irrespective of whether that gradient is of the same or opposite sign to that of the drug), the permeability of the skin to scopolamine is increased by one to two orders of magnitude. Microscopic examination of the skin subjected to such treatment reveals marked swelling, distortion, and intercellular delamination of the stratum corneum, which is only partially reversible following complete extraction with water. These effects are believed due to development of very high osmotic stresses produced within the stratum corneum, as both water and DMSO are transported into the tissue. SCOPEThis paper is the third in a series devoted to the measurement and interpretation of the transport of relatively small, biologically active molecules though intact human skin, who3e objective has been to explain the often puzzling barrier properties of skin on rational, physicochemical principles of solution thermodynamics and molecular diffusion kinetics.For many years, certain super solvents such as dimethyl sulfoxide (DMSO) have been recognized as exceedingly skin-permeable substances and have been shown to greatly elevate the permeability of skin to many compounds to which intact human skin is normally an effective barrier.These observations have evoked numerous hypotheses about the role of substances such as DMSO on skin permeation, some of which call upon active transport mechanisms, or coupled-flow, piggyback diffusion processes, which have few, if any, counterparts in passive membrane transport systems.In the studies herein reported, we have found that the effects of DMSO on skin permeability in vitro are entirely consistent with accepted theories of solution diffusion models of membrane transport, when changes in penetrant activity with changes in solvent composition are properly allowed for, and when changes in tissue microstructure accompanying osmotic shock are duly considered. CONCLUSIONS A N D SIGNIFICANCEThe principal barrier to the transport of drugs and other relatively small molecules through intact human skin is localized with the stratum corneum, which is comprised of dead, keratinized, partially desiccated epidermal cells. Drug permeation through the stratum corneum occurs principally by a passive diffusion process independent of metabolic assistance...

Penetration of guinea pig skin by acyclovir in different vehicles and correlation with the efficacy of topical therapy of experimental cutaneous herpes simplex virus infection

“…Examples include urea, alcohol-water mixtures, and DMSO (4,20). ACV-PEG and 100 ,u.l of 0.5% ACV in DMSO were applied to the exposed skin surface of the diffusion apparatus.…”

Effects of Freezing on Functionality and Physicochemical Properties of A 3D-Human Skin Model

“…Nevertheless, cryopreservation at lower temperatures requires the use of cryopreservation agents such as DMSO and glycerol to help the conservation of cells' integrity. As our studies are considered in a perspective of pharmaceutical testing, use of these cryopreservation agents should be avoided because they are known to increase skin permeability [52,53].…”

Transdermal delivery of peptide and protein drugs: An overview

“…The stratum corneum structure can be disrupted either chemically or physically. The disruption may affect both intracellular and extracellular structure (Rhein et al, 1986) and may arise as a result of protein denaturation (Scheuplein and Ross, 1970;Wood and Bettley, 1971;Weiner et al, 1972;Kurihara-Bergstrom et al, 19861, fluidization and disorganization or extraction of the extracel-Mar lipid lamellae (Wood and Bettley, 1971;Emberry and Dugard, 1971;Rhein et al, 1986;Golden et al, 1987;Hoogstraate et al, 1991), or delamination of the extracellular lipids via osmotic pressure (Chandrasekaran et al, 1977).…”

“…For example, DMSO produces a burning sensation as well as localized irritation (Kligman, 19651, and at high concentrations can produce erythema (superficial inflammation of the skin in patches) and weals (Hadgraft, 1984). Since significant enhancement of permeation rates using DMSO are only obtained at concentrations greater than 65% (Chandrasekaran et al, 1977;Kurihara-Bergstrom, 1986) this limitation effectively rules out its use as a transdermal enhancing agent. Anionic surfactants have also been found to cause skin irritation (Wood and Bettley, 1971;Novak and Francom, 1984;Sherertz et al, 1987).…”