Deposition of salicylic acid into hamster sebaceous.

In an earlier paper, we identified vehicles that are miscible with sebum, using differential scanning calorimetry (DSC). In this paper, the potential of these vehicles to deliver salicylic acid (SA) into the sebum-filled follicles of hamster ears is examined. The main objective of this study is to correlate the melting transitions of a model sebum with the follicular delivery of SA, using two different types of vehicles (fatty and polar). Generally, the fatty vehicles show higher deposition than the polar vehicles. Follicular delivery of salicylic acid correlates well with its solubility in the respective vehicles. This extent of deposition also shows a relationship with the effect of the vehicle on thermal behavior of the model sebum. The nature of the relationship depends on the vehicle (polar or fatty) tested. We conclude that DSC could be used to identify appropriate vehicles for drugs whose follicular delivery depends on solubility. The results also suggest that delivery into the sebaceous glands occurs by two different mechanisms, depending upon the polarity of the vehicle and the physicochemical properties of the drug. The results of these experiments are further extended to investigate follicular delivery of SA from two different types of oil-in-water emulsion formulations. From these studies we conclude that either increasing the volume of the oil phase or changing the emulsion to a water-in-oil emulsion would increase follicular deposition. Our research highlights the role of sebum, its compatibility with drug molecules, and vehicle selection in the transport of drugs into the follicles. The overall results of these experiments provide a reasonable understanding of the mechanisms underlying the transport of drugs to, and subsequently through, the sebaceous follicle.

Differential scanning calorimetry studies of sebum models.

Human sebum is a mixture of triglycerides, fatty acids, wax esters, squalene, cholesterol, and cholesterol esters. P. acnes, a bacterium that is normally found on the skin, hydrolyzes certain triglycerides to fatty acids, thereby changing the sebum composition. The objective of this study was to examine the physical state of a model sebum and the effect of variations in its composition on its physical properties including (a) the carbon chain length of the components, (b) the ratio of unsaturated to saturated components, and (c) the ratio of triglycerides to fatty acids. A model sebum mixture was prepared based on a composition reported in the literature and evaluated by differential scanning calorimetry (DSC). Since cholesterol and cholesterol esters contribute insignificantly to sebum composition, they were not included. Squalene was kept constant (13%), while the concentration of the rest of the components was varied. Variations of sebum were prepared by dissolving all components in a 3:1 chloroform-methanol mixture for uniformity. Subsequently the solvent was evaporated at room temperature. The samples were then analyzed using DSC. Four distinct endotherms (namely, Mp-1, Mp-2, Mp-3, and Mp-4) were observed between -50 degrees C and 100 degrees C. Mp-1 and Mp-2 occurred below 0 degrees C and were contributed by unsaturated components. Mp-3 and Mp-4, which represent the saturated components, occurred above 30 degrees C. Thus, at normal skin temperature (skin surface temperature is 32 degrees C), sebum contains both a solid and a liquid phase. All the transition temperatures increased with an increase in carbon chain length for the same ratio of unsaturation to saturation. A replacement of unsaturated components with corresponding saturated components led to a decrease in the transition temperatures for the former (Mp-1 and Mp-2) and an increase in the transition temperatures for the latter (Mp-3 and Mp-4). Replacement of triglycerides with corresponding fatty acids (mimicking the action of anaerobic bacteria) caused an increase in Mp-2 and a decrease in Mp-4. In all cases, the final melting temperature (Mp-4) was greater than the temperature of the human skin surface (32 degrees C); thus components contributing to these endotherms are still solids at skin temperature. All variations in the sebum model led to mixtures of solids and liquids at skin temperature. Considering a reduction in Mp-3 and/or Mp-4 to represent sebum "fluidization," it was achieved by a decrease in carbon chain length, an increase in unsaturation, or a substitution of triglycerides by corresponding fatty acids. Preferential enrichment with the saturated species will lead to enrichment of solids versus liquids in the sebum, presumably making it difficult for the liquid phase to dissolve the solids. It seems plausible that perturbation of the balance of solid and liquid components of sebum, such as by P. acnes action, may lead to blockage of the follicle. Future research will investigate strategies to dissolve and/or liquify the solid phase of sebum.