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.

Zika (ZIKV), La Crosse (LACV), and Cache Valley (CVV) viruses are mosquito-vectored diseases that cause significant morbidity and mortality in humans and animals. Transmission of these viruses are dependent on numerous factors including vector competence and the effects of mosquito-virus interactions. We conducted vector competence studies of local Aedes and Culex mosquitoes for ZIKV and CVV, and found that all Aedes mosquitoes were competent for CVV and only Aedes albopictus and Aedes japonicus were competent for ZIKV. Vector competence for CVV was dose-dependent, where mosquitoes orally infected with high titers developed higher transmission rates. We also found that vector competence for ZIKV was limited by midgut and salivary gland barriers. Second, we looked at the effects of LACV and ZIKV infection on repellent response in Aedes mosquitoes and found that infected mosquitoes were refractory to low concentrations of DEET, picaridin, and PMD. Increasing concentrations of the repellents to ≥10% was able to increase percent protection (%p) against infected and uninfected mosquitoes. Lastly, we determined the effects of ZIKV and LACV infection on oxidative stress and glutathione-S-transferase (GST) activity in Aedes albopictus. Virus infection had no effect on oxidative stress, but GST activity was significantly different for mosquitoes 3-days post-exposure. We found that oxidative stress levels and GST activity had an inverse relationship for infected and uninfected mosquitoes, where oxidative stress decreased and GST activity increased over the 10-day test period. This indicates that GSTs may aid in controlling byproducts of oxidative stress. The results from this entire study identified competent vectors for emerging arboviruses and demonstrated the behavioral and physiological effects of virus infection in the mosquito vector. / Doctor of Philosophy / Zika (ZIKV), La Crosse (LACV), and Cache Valley (CVV) viruses are transmitted by mosquitoes and can make humans and animals very sick. There are many biological factors that determine if a mosquito can transmit a virus and these viruses can change the biology of a mosquito. We conducted laboratory studies to see if Aedes and Culex mosquitoes can transmit ZIKV and CVV. We found that all Aedes mosquitoes were able to transmit CVV and only the Asian tiger mosquito and Asian rock pool mosquito were able to transmit ZIKV. Mosquitoes infected with high amounts of CVV developed higher transmission rates. We also found that transmission of ZIKV was limited by barriers in the mosquito midgut and salivary glands. Second, we looked at the effects of LACV and ZIKV infection on how Aedes mosquitoes respond to repellents and found that infected mosquitoes were less sensitive to low concentrations of DEET, picaridin, and PMD. Increasing concentrations of the repellents to 10% or higher was able to provide adequate protection against infected and uninfected mosquitoes. Lastly, we determined the effects of ZIKV and LACV infection on oxidative stress and glutathione-S-transferase (GST) activity in the Asian tiger mosquito. Virus infection did not change oxidative stress, but GST activity was higher in infected mosquitoes tested after 3 days after infection. We found that oxidative stress decreased and GST activity increased over the 10-day test period. This indicates that GSTs may help control damaging products from oxidative stress. The results from this entire study identified what mosquitoes were able to transmit emerging mosquito-borne viruses and demonstrated the biological effects of virus infection in the mosquitoes.