Master of Science (MS), Wright State University, 2023, Pharmacology and Toxicology

The skin is exposed to a variety of external stressors, from irritants to toxic agents to ultraviolet radiation (UVR). While mice and human volunteers can be used for research studies, there are limitations in the range of environmental stressors that can be studied using these models. Therefore, our research team has been investigating the use of human skin explants as a model to study the immediate effects of environmental stressors ex vivo. Although this method has been successful, obtaining fresh human skin for these studies is difficult due to limited availability. To overcome this issue, we are evaluating the possibility of using porcine skin explants in our model systems. The primary advantage of using porcine skin is that it is readily available in large quantities, and its structure bears many similarities to that of human skin. In our research, we have found that various stressors, including UVB radiation, can trigger the production of Platelet-Activating Factor (PAF) in the skin. This, in turn, activates the enzyme acid sphingomyelinase (aSMase), leading to the shedding of subcellular microvesicle particles (MVP). In our research studies, we have used various models, such as cell lines, mice, human skin explants, and limited studies in human volunteers. Currently, we are examining the possibility of using porcine skin explants as a model to study MVP release in response to different types of stressors that are relevant to the skin. The application of the carbamyl PAF agonist PAF (CPAF) or a phorbol ester topically to the skin leads to an increase in MVP release. Similarly, exposing the skin to different UVB fluences also results in a higher release of MVP. Our experiments on porcine skin explants show similar results to human skin explants in terms of MVP release, although porcine skin appears to be less reactive to these agents. Although porcine skin shares many structural similarities with human skin, unlike human skin and cell lines, the combined impac (open full item for complete abstract)

Committee: Jeffrey B. Travers M.D., Ph.D. (Advisor); David Cool Ph.D. (Committee Member); Yangfang Chen M.D., Ph.D. (Committee Member) Subjects: Pharmacology; Toxicology

MS, University of Cincinnati, 2019, Pharmacy: Pharmaceutical Sciences

Permeation studies are an essential tool in ensuring the efficacy of topically applied drugs and in studying the absorption of toxic compounds. There are many factors that can affect permeation studies such as the choice of solvent, the physiochemical properties of the drug, and skin donor conditions. In this study, we aimed to investigate two of these aspects in permeation studies: dose effect and impact of skin furrows. In skin permeation studies, the rate of skin penetration of a compound is not necessarily proportional to the applied dose. In this thesis research, the dose dependence effect on skin permeation was determined in Franz diffusion cell under finite dose conditions. Radiolabeled solutions of urea, dexamethasone, estradiol, caffeine, and ethylene glycol were prepared in ethanol at doses ranging from 0.1 -200 μg. A 72-h study was conducted, and the receptor solution was sampled at various time points. The percent absorbed was calculated and analyzed in terms of the applied dose. The result showed a dose dependence effect on caffeine, dexamethasone, and estradiol up to a dose of 100 μg. No dose dependence was observed in the permeation profiles of urea and glycerol. Another factor investigated was the presence of furrows on the skin surface. These furrows might lead to erroneous interpretation of the results in skin permeation studies using tape stripping, in which the material trapped in the furrows removed by the tapes representing the deeper layers of the SC might be interpreted as the material permeating within these layers. The objective of this study was to investigate the effect of skin furrows on tape stripping results. Non-penetrating fluorescent materials were topically applied to split-thickness human and full-thickness porcine skin samples. Tape stripping was applied, and the tapes were assessed by fluorescence microscopy and quantitative analyses. The microscopic images were assessed visually to determine the presence of the applied mat (open full item for complete abstract)

Committee: Kevin Li Ph.D. (Committee Chair); Kavssery Ananthapadmanabhan Ph.D. (Committee Member); Gerald Kasting Ph.D. (Committee Member) Subjects: Pharmaceuticals