The skin is a complex membrane that performs many physiological functions such as metabolism, synthesis, temperature regulation, and excretion. Its upper layer, the stratum corneum, is considered to be the main barrier to the percutaneous penetration of exogenous materials. This barrier is also important in the maintenance of water within the body as well as in the absorption of pharmaceutical and other agents. There are several categories of pharmaceutical products that are targeted to the skin or utilize the skin as a port of entry into the body and these include transdermal drug delivery systems (patches), gels, creams, ointments, lotions, as well as subcutaneous implants and dermal vaccinations. In contrast to the traditional oral route, the use of transdermal drug delivery by-passes first pass metabolism of the liver, the extreme pH environments of the gastrointestinal tract, and problems of absorption in the stomach, which often contains food, resulting in erratic and pulsed delivery of drugs into the intestine and variability in plasma concentration-time profiles. As with other routes of delivery, transport across the skin is also associated with several disadvantages, the main drawback being that not all drugs are suitable candidates. A number of physicochemical parameters have been identified (such as molecular weight) that influence the diffusion process, and variations in permeation rates can occur between different skin models, patients, different races, and between young and old. The major challenge is overcoming the resistance of the skin to permeation in a reversible and non-damaging manner as well as the design of therapeutically effective topical and transdermal formulations.
Dr. Michniak-Kohn’s main research focus lies in the area of topical, transdermal, and buccal drug delivery. Her group is involved in the design and testing of novel dermal penetration enhancer and retardant compounds, investigation of their mechanisms of action and transport through the skin layers, molecular and computational modeling of percutaneous absorption as well as optimization and testing of topical and transdermal formulations. Studies involve novel carrier systems such as nanospheres and investigation of skin transport pathways using confocal microscopy, SEM, TEM, Raman, and FT-IR. Physical drug delivery enhancement techniques are also being studied, such as iontophoresis and the use of microneedles.
Several projects involve a tissue engineered full-thickness human skin model which has been shown to possess similar drug permeability to human skin. Projects include evaluation of correlations between the drug permeability, stratum corneum lipid composition/organization, growth media composition, immunohistochemistry, and morphology and gross structure of the bioengineered skin. In addition, novel polymer dermal scaffolds are being tested in the model to improve its mechanical strength. Additional studies involve the effects of protective barrier creams and other formulations on the penetration of chemical warfare agent mimics, insecticides, pharmaceutical, and cosmetic actives using the skin models.
Part of the work includes in vivo pharmacokinetic and metabolic studies with drugs administered by several routes (topical, intravenous-infusion, bolus, and oral). In addition, the Michniak Group is part of the $15M Rutgers NSF Engineering Research Center examining the scientific foundation, based on a predictive understanding of structure-function-performance relationships, for the optimal design of structured organic composites with advanced functionality. The work involves drug release and dissolution of pharmaceutical dosage forms including tablets and orally administered polymeric films.