PubMed · 14281091
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D W MILLS, G L OLIVER. 1965-05-15. CORTICOSTEROID GLAUCOMA.. https://pubmed.ncbi.nlm.nih.gov/14281091/
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Perillyl alcohol (POH) is a relatively non-toxic agent that has been shown to be a promising anticancer monoterpene in preclinical models. Studies have indicated that topical application of POH may prove to be effective as a skin cancer chemoprevention therapy. The main aim of this study was to determine the influence of several factors on the stability of POH in solution and develop a topical formulation of POH. During preformulation, the influence of pH, temperature, ionic strength, and organic solvents, on the stability of POH was evaluated at four different temperatures: 4, 25, 37, and 48 degrees C. POH was found to degrade under acidic conditions with degradation following apparent first-order kinetics. A hydrophilic topical cream formulation of POH was developed and prepared for toxicology and clinical studies. A reverse phase gradient HPLC method was developed to quantitate POH in the complex formulation. Stability studies of the formulation and a placebo were performed and the formulation was found to be physically and chemically stable over a period of 1 year at 4 and 25 degrees C.
Topically applied ethanol is a well-known dermal penetration enhancer. The purpose of this work was to determine if ethanol consumption might also increase transdermal penetration. Male rats were fed either an ethanol containing or control diet for 6-8 wk. After the feeding regime was completed, skin was removed and placed in an in vitro diffusion system. The transdermal absorption of four very commonly used herbicides was determined. Penetration through skin from ethanol-fed rats was enhanced when compared to control by a factor of 5.3 for paraquat, 2.4 for atrazine, and 2.2 for 2,4-dichlorophenoxyacetic acid (2,4-D), and reduced by a factor 0.6 for trifluralin. Comparison of physical factors of the herbicides to the penetration enhancement revealed an inverse linear correlation with lipophilicity, as defined by log octanol/water partition coefficient (log Kow) with r2 =.98. These changes were at least partially reversible after 1 wk of abstinence from ethanol. These experiments demonstrate that regular ethanol consumption can alter the properties of the dermal barrier, leading to increased absorption of some chemicals through rat skin. If ethanol consumption has the same effect on human skin it could potentially have adverse health effects on people regularly exposed to agricultural, environmental, and industrial chemicals.
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