Penetration enhancement dimethyl sulfoxide

Caspers, P.J., et al. 2002. Monitoring the penetration enhancer dimethyl sulfoxide in human stratum corneum in vivo by confocal Raman spectroscopy. Pharm Res 19 1577. 

Anigbogu, A. N. C. et al. Fourier-transform Raman spectroscopy of interactions between the penetration enhancer dimethyl-sulfoxide and human stratum comeum. International Journal of Pharmaceutics 725(2) 265-282, 1996. 

Fig. 6.14. Label-free chemical imaging of the penetration pathways for the topically applied drug diffusion enhancer dimethyl sulfoxide (DMSO) into mouse skin tissue Dual-frequency SRS imaging tuned into the characteristic vibration of DMSO at 670 cm-1 (bright gray regions) and the CH2 vibration of lipid-rich adipocytes at 2845 cm-1 (dark gray regions) at a depth of 65pm into the tissue. DMSO is hydrophilic and hence avoids lipid structures such as adipocytes (Image courtesy of Brian Saar, Chris Freudiger, and Wei Min [12])...

Solvents have been added to nerve agents to facilitate handling, to stabilize the agents, or to increase the ease of percutaneous penetration by the agents. Percutaneous enhancement solvents include dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylpalmitamide, N,N-dimethyldecanamide, and saponin. Color and other properties of these solutions may vary from the pure agent. Odors will vary depending on the characteristics of the solvent(s) used and concentration of nerve agent in the solution. 

Apart from this classic approach, it would be possible to improve the properties of known CWs, e.g. microencapsulation so that less stable or highly volatile substances can be used. Nanotechnology offers new possibilities, as described recently by Price and Peterson (2008). The other option is to improve penetration using known enhancers like dimethyl sulfoxide (DMSO). While the percutaneous toxicity (expressed as LD50 in rats) of one of the toxic organophosphates - O-isopropyl 5-2-diisopropylaminoethyl methyl phosphnothiolate - is 59.1 P-g/kg, in mixture with DMSO this value is decreased to 10.1 pg/kg (Bajgar, 1989). 

Dimethyl sulfoxide enhances the skin penetration of several drugs, which may result in producing the adverse effects associated with those drugs. 

Dimethyl sulfoxide (DMSO) has excellent solvent properties and acts as a skin penetration enhancer for drugs and other substances by increasing the permeability of the barrier layer of the skin. It is used in the topical administration of drugs, the production of synthetic fibers, the application of pesticides, as an antifreeze, hydraulic fluid, and in the manufacturing of industrial cleaners and paint strippers. Its antiinflammatory and analgesic effects, and the ability to quench free radicals have been by physicians and others for various therapeutic uses. 

One approach is to use penetration enhancers such as dimethyl sulfoxide (DMSO) [150-153]. DMSO may play a dual role, since it also may facilitate the differentiation of certain types of malignant cells and thus alter their response to exogenous ALA [154]. 

Penetration into the skin can be enhanced by penetration enhancers. These excipients diffuse into the stratum comeum and interact with components of this layer. The barrier function of the skin decreases. The effect of penetration enhancers is based on two mechanisms. The penetration enhancer can change the stracture of the stratum comeum or the solubility of the active substance in the skin. Penetration enhancers should not damage the underlying skin layers and should not be toxic or allergenic. Moreover, the effect must be reversible. Because of the different properties and mechanisms of action of penetration enhancers it is difficult to predict which enhancer will be most effective for the penetration of a specific active substance. Substances such as dimethyl sulfoxide (DMSO), salicylic acid, urea, propylene glycol, ethanol, isopropyl alcohol and many acids can act as penetration enhancers. 

For a good therapeutic effect the choice of the active substance and the choice of the vehicle are important. Physical and chemical factors play an important role. The solubility of the active substance in the vehicle and the concentration, the size of the molecule of the active substance, the partition between vehicle and skin, the particle size (in case of suspensions) and the nature of the vehicle (aqueous or lipid) determine the penetration speed and depth. Hydrocortisone, for example, is more lipid soluble in the ester form (hydrocortisone acetate). The latter will penetrate into the skin faster and more complete. Hydrocarbons, such as soft and liquid paraffin, release lipophilic active substances only very slowly and substances formulated in these bases will penetrate only in limited amounts into the skin. Fatty oils (vegetable oils, triglycerides) are able to pass into the upper layers of the skin. Penetration enhancers (salicylic acid, dimethyl sulfoxide, propylene glycol, urea) increase the penetration of active substances into the skin. 

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