A novel encapsulation favorably modifies the skin disposition of topically-applied N,N-diethyl-3-methylbenzamide (DEET)

The skin disposition of the insect repellent N,N-diethyl-3-methylbenzamide (DEET) was modified using a unique encapsulation method. Incorporation of DEET into a controlled-release microcapsule facilitated a decrease in skin absorption compared to a DEET in ethanol control while evaporation rates were maintained. Although DEET is considered to be a safe active in topical formulations, it is important to minimize skin absorption in order to retain the material on the skin surface for effective repellency via evaporation. Repellents must evaporate to maintain an effective vapor concentration at the skin surface in order to repel insects away from a host. Microcapsules were constructed using an interfacial precipitation method to form an oriented polysaccharide film around dispersed lipid droplets. Specifically, the shell was composed of reacted sodium carboxymethylcellulose and benzalkonium chloride while the core consisted of a mixture of emulsifiers, polyamide resin and acetyltributyl citrate which form a gel in which DEET (15% w/w) was confined. Measurements were made using human cadaver skin and modified Franz diffusion cells which allowed for simultaneous sampling of both skin absorption and evaporation. Quantitative DEET analysis was performed using HPLC. After 48 hours, microencapsulation led to a 30% reduction in DEET permeation along with a 36% increase in cumulative evaporation for a 3 µL (0.57 mg/cm² DEET) dose compared to the ethanol control. In vitro vapor trapping measurements also demonstrated that encapsulation provided more than 48 hours of effective evaporation for repellency, while the control provided less than 15 hours. As the dose was increased from 3 µL to 20 µL (0.57 mg/cm² to 3.8 mg/cm² DEET) the reduction in absorption also increases from 34% to 51% compared to an ethanolic control. Using the same microcapsule shell and altering the core to a simple lipid-DEET mixture showed absorption kinetics similar to the ethanol control but with 40% higher evaporation rates. A shell-less microcapsule, but with the same core components, formulated as an aqueous suspension, was also tested against an ethanol control formulation. The shell-less microcapsule was not significantly different from the original microcapsule, reducing absorption by 30% and increasing evaporation by 34% compared to the control. To further reduce DEET skin absorption, a skin washing procedure was implemented. At 4 hours post dose, samples were washed with one of three washing solution. Microencapsulated DEET had 76% reduction in absorption compared to an ethanolic DEET control. Regardless of the washing procedure used, DEET absorption and absorption flux was further reduced with encapsulation. The combination of these experiments shows that a novel encapsulation favorably modifies the skin disposition of topically-applied DEET.

Name thesis:degree_name

PhD

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Pharmacy: Pharmaceutical Sciences/Biopharmaceutics

Grantor dc:publisher

University of Cincinnati

Year dc:date

2012

Author dc:creator

• Karr, Jennifer I.

Contributors dc:contributor

• Kasting, Gerald

• Pharmaceuticals
• Microencapsulation
• DEET
• Percutaneous absorption
• Skin permeation

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=ucin1353154812

OAI identifier oai:identifier

oai:etd.ohiolink.edu:ucin1353154812