| The topical route provides localized delivery for many skin diseases. The objective of this study was to determine the feasibility of intradermal delivery of a novel lipophilic molecule, PTTC, as a potential psoriasis therapy. Microneedles were utilized to bypass the stratum corneum and achieve delivery to the viable epidermis. In vitro cell culture techniques were used to assess the skin irritation potential of PTTC and a psoriatic cell culture was dosed to determine efficacy by measurement of IL-6. The results show PTTC delivery could be achieved with use of microneedles, and the molecule was found to be non-irritant and efficacious in downregulating IL-6 in psoriatic skin. As many topical products are intended for skin diseases with damaged barrier, in vitro models simulating compromised skin were investigated, using diclofenac diethylamine as a model compound. Human cadaver skin treated with delipidization solvent, insertion of microneedles, or tape stripping was used as models to simulate damaged skin. Permeation studies were carried out on Franz diffusion cells using a lipophilic and hydrophilic vehicle for comparison. The results show delivery is greater with a hydrophilic vehicle across and correlates with degree of barrier impairment. In addition to simulating compromised skin, clinical usage of topical products can also be mimicked in vitro. A gel was rubbed into human cadaver skin, applied multiple times a day, and varying strengths were tested to determine effect on delivery. Diclofenac permeation was found to be concentration dependent, and significantly increased with multiple applications. The transdermal delivery route can bypass first pass metabolism. However, permeation is limited to small, moderately lipophilic compounds. Active techniques, such as microneedles or iontophoresis, can enhance the delivery of charged molecules that may not permeate well passively. Glycopyrrolate is a quaternary amine with an inherent positive charge. Each of these techniques was applied to a drug solution and permeation studies were performed on Franz cells. The results indicate iontophoresis alone enhanced delivery, and no synergism was observed for combination of both techniques. In conclusion, in vitro methods of Franz cells and cell culture models are powerful tools to determine drug delivery into and across skin. |
