The molecular basis of the potent transdermal enhancement activity of a series of iminosulfuranes, structure provided where X = H, Cl, Br, and I, is being investigated skin models. It has been shown (J. Lipid Res. 46(2005), 2192-2201.) that correlations exist between the activity of the aforementioned transdermal penetration enhancers (TPE) and the extent to which these agents bind to DMPC vesicles and perturb the gel to liquid crystal phase transition measured by calorimetry. The degree to which the perturbation of these compounds extends into the bilayer interior in contrast to surface activity is unclear. To gain insight into this issue, the 31P NMR resonance from DMPC and DMPC-cholesterol unilamellar vesicles have been split by the slowly penetrating paramagnetic metal ion Pr+3. The extent to which this perturbation is attenuated by transdermal penetration enhancers has been investigated as a function of Pr+3 exposure time and iminosulfurane concentration. The effect of these iminosulfuranes on bilayer integrity is also being explored by monitoring the induced release of carboxyfluorescein from DMPC and DMPC- cholesterol unilamellar vesicles.

Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Petr Tirala Supervisor: PharmDr. Barbora Švecová, Ph.D. Title of thesis: Formulation and (trans)dermal application of liposomes containing imiquimod Imiquimod (IMQ), a substance belonging to the class of heterocyclic imidazoquinolines, shows significant immunomodulatory effects after topical administration, which is used to treat a variety of viral and malignant diseases of the skin. IMQ is currently used in clinical practice in the form of cream Aldara® containing 5% of active substance, which is unstable and irritating and after removal from the skin IMQ poses an ecological load for the environment. The aim of this thesis was preparation of liposomes for topical administrativ containing lower - 1% amount of IMQ and evaluation of penetration of IMQ into human skin in vitro. To improve the properties of liposomes and promote patency of the active ingredient through the skin barrier to the deeper skin layers various additives were used. Permeation experiments were carried out in Franz diffusion cells on the human skin in order to create the conditions that are as physiological as possible. Amount of IMQ was determined in the uppermost layer of the skin, epidermis, dermis, acceptor phase...

This work deals with the transmittance of a family of non-steroidal anti-inflammatory drugs across biological membranes in combination with the use of hyaluronan. Hyaluronic acid (hyaluronan, HYA) is a linear polysaccharide formed from disacharide units containing N-acetyl-D-glucosamine and glucuronic acid. HYA is present in almost all biological fluids and tissues, so there is an assumption that could affect the penetration of substances through the skin. Standards were prepared by anti-inflammatory drugs in admixture with various concentrations hyaluronan and subsequently measured transmittance of such substances through the skin. Standards were applied to the skin obtained from pig auricle. The drug content was determined by HPLC.