In this thesis, a series of in vitro diffusion studies were performed to evaluate the transmembrane permeation of picaridin and oxybenzone across human epidermis and poly(dimethylsiloxane) (PDMS) membrane. Transdermal permeation of picaridin and oxybenzone from four commercially available repellent and sunscreen products was also investigated by using different application concentrations and sequences. The results obtained were then compared to those of the repellent DEET and the sunscreen oxybenzone under identical experimental conditions. Permeation of picaridin and oxybenzone across human epidermis was suppressed when both compounds were used concurrently. Increasing concentration of the test compounds further reduced the permeation percentage of picaridin and oxybenzone. While permeation characteristics were correlative between human epidermis and artificial PDMS membrane, permeability of PDMS membrane was significantly larger than that of human epidermis. This finding was different from concurrent use of DEET and oxybenzone in which a synergistic permeation enhancement was observed between the two substances. Transdermal permeation of picaridin across human epidermis from various commercially available spray preparations was significantly lower than that of DEET from similar spray products, both alone and in combination with sunscreen oxybenzone. Concurrent application of the commercial products resulted in either no change or suppression of permeation of picaridin and oxybenzone. This finding was also different from concurrent application of DEET and oxybenzone using commercial preparations. In addition, permeation of picaridin and oxybenzone across human epidermis was dependent on application concentration, use sequence, and preparation type.It was concluded from this thesis that picaridin would be a better candidate for concurrent application with sunscreen preparations in terms of percutaneous permeation.

In this thesis, a series of in vitro diffusion studies were performed to evaluate the transmembrane permeation of picaridin and oxybenzone across human epidermis and poly(dimethylsiloxane) (PDMS) membrane. Transdermal permeation of picaridin and oxybenzone from four commercially available repellent and sunscreen products was also investigated by using different application concentrations and sequences. The results obtained were then compared to those of the repellent DEET and the sunscreen oxybenzone under identical experimental conditions. Permeation of picaridin and oxybenzone across human epidermis was suppressed when both compounds were used concurrently. Increasing concentration of the test compounds further reduced the permeation percentage of picaridin and oxybenzone. While permeation characteristics were correlative between human epidermis and artificial PDMS membrane, permeability of PDMS membrane was significantly larger than that of human epidermis. This finding was different from concurrent use of DEET and oxybenzone in which a synergistic permeation enhancement was observed between the two substances. Transdermal permeation of picaridin across human epidermis from various commercially available spray preparations was significantly lower than that of DEET from similar spray products, both alone and in combination with sunscreen oxybenzone. Concurrent application of the commercial products resulted in either no change or suppression of permeation of picaridin and oxybenzone. This finding was also different from concurrent application of DEET and oxybenzone using commercial preparations. In addition, permeation of picaridin and oxybenzone across human epidermis was dependent on application concentration, use sequence, and preparation type.It was concluded from this thesis that picaridin would be a better candidate for concurrent application with sunscreen preparations in terms of percutaneous permeation.

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are commonly incorporated into commercially available repellent and sunscreen preparations. Both compounds have demonstrated an increased percutaneous permeation and systemic disposition after concurrent application in vitro and in vivo. The permeation enhancement between DEET and oxybenzone not only compromises their respective protective efficacy against biting insects and UV radiation, but also potentiates toxicological properties in susceptible subjects. The pharmacokinetic and toxicological profiles from concurrent use of DEET and oxybenzone were evaluated and compared in this thesis. DEET and oxybenzone were administered by intravenous and topical routes in rats, either alone and/or in combination, to compare the pharmacokinetics of parent compounds and their primary metabolites in vivo. To evaluate toxicological characteristics, rat primary cortical neurons and astrocytes, and rat hepatoma 1548 cells were exposed to DEET, oxybenzone and their metabolites in vitro, and cell viability was analyzed. Various behavioral testing protocols were also performed to assess arousal, locomotion, habituation, and motor coordination of rats over a 30-day study period. Concurrent topical application of DEET and oxybenzone enhanced the disposition of DEET and its metabolites in rats, but did not consistently affect the distribution of oxybenzone and its metabolites. The disappearance of DEET from skin application site was accelerated; its apparent elimination half-life was decreased while its plasma and tissue concentrations were predominantly increased. Cellular toxicity occurred at 1 μg/ml for neurons and 7-day exposure for both astrocytes and neurons. Viability of hepatoma cells was also reduced when treated with DEET, oxybenzone and their metabolites, either alone or in combination, most notably after 72 hours of exposure. However, no overt signs of toxicity were observed from behavioral testing in rats after a 30-day topical study. The pharmacokinetic data obtained was beneficial in understanding and elucidating absorption and biodistribution of DEET and oxybenzone in vivo. The toxicological data suggested that the risk for increasing adverse effects from concurrent skin application of repellents and sunscreens would be low and marginal in healthy individuals. Nevertheless, further studies should be carried out to assess the long-term health impact of these compounds in susceptible subjects, especially at higher application doses.