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Nanoemulsions (NEs) are used as transdermal drug delivery systems for systematic therapeutic purposes. We hypothesized that the skin permeation profile of an NE could be modulated by incorporating it into a hydrogel containing differing proportions of thickening agent. The objectives of this study were as follows: 1) to determine the stability and skin irritability of NE gels (NGs) containing 1%, 2%, and 3% (w/w) Carbopol ® 934 (CP934) (termed NG1, NG2, and NG3, respectively); 2) to compare the skin permeation profiles and drug deposition patterns of the NGs; and 3) to visualize the drug delivery routes of the NGs. Terbinafine and citral were incorporated into the NGs as model drugs. Ex vivo skin permeation tests indicated that the percutaneous flux rates of terbinafine decreased in the order NE (215 μg/cm 2 ) &gt; NG1 (213 μg/cm 2 ) &gt; NG2 (123 μg/cm 2 ) &gt; NG3 (74.3 μg/cm 2 ). The flux rates of citral decreased in the order NE (1,026 μg/cm 2 ) &gt; NG1 (1,021 μg/cm 2 ) &gt; NG2 (541 μg/cm 2 ) &gt; NG3 (353 μg/cm 2 ). The NGs accumulated greater amounts of the drugs in the stratum corneum and less in the epidermis/dermis than did the NE ( P &lt;0.05) over a period of 12 h. Laser scanning confocal microscopy indicated that the NGs altered the main drug delivery routes from skin appendages to intercellular paths. Histological images suggested that perturbations to the skin structure, specifically the size of the epidermal intercellular spaces and the separation distance of dermal collagen bundles, could be significantly minimized by increasing the proportion of CP934. These results suggest that adjustments of the CP934 proportions can be used to modulate the skin permeation profiles of NGs for specific therapeutic purposes.

international journal of nanomedicine

Effects of Carbopol&lt;sup&gt;&amp;reg;&lt;/sup&gt; 934 proportion on nanoemulsion gel for topical and transdermal drug delivery: a skin permeation study