title: Dermal targeting of tacrolimus using colloidal carrier systems.
abstract: In the therapy of chronic inflammatory skin diseases, the epicutaneous application of anti-inflammatory drugs in combination with maintenance therapy leads to ideal therapeutic long term effects. In this work, the development of well-tolerated colloidal carrier systems (ME) containing tacrolimus is described. A comprehensive physico-chemical characterization of the novel systems was performed using different techniques. The potential of three ME compared to an ointment as suitable carrier for dermal delivery of tacrolimus was determined. The penetration studies demonstrated that in comparison to the standard vehicle ointment, all three ME resulted in higher concentrations of tacrolimus in the deeper skin layers independent of the time of incubation. Particularly, the percentage of the bioavailable amount of tacrolimus (sum of the amount found in the dermis and acceptor compartment) from the ME with concentrations up to 20.95 ± 12.03% after 1000 min incubation time differed significantly (p<0.01), when compared to the ointment which yielded a concentration of 6.41 ± 0.57%. As a result of these experiments, using colloidal carrier systems, the penetration profile of tacrolimus was enhanced significantly (p<0.01). High drug amounts penetrated the target site in a short period of time after applying the ME.
authors.affiliation: Faculty of Biosciences/Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Straße 4, 06120 Halle, Saale, Germany.alexandra.goebel@pharmazie.uni-halle.de
authors.forename: Alexandra S B
authors.initials: AS
authors.lastname: Goebel
authors.forename: Reinhard H H
authors.initials: RH
authors.lastname: Neubert
authors.forename: Johannes
authors.initials: J
authors.lastname: Wohlrab
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects; D003102:Colloids; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D005960:Glucosides / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D054709:Lecithins / Q000737:chemistry* / Q000633:toxicity; D008027:Light; D009824:Ointments; D010539:Permeability; D012542:Scattering, Radiation; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D016559:Tacrolimus / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000893:Anti-Inflammatory Agents; D003102:Colloids; D004337:Drug Carriers; D005960:Glucosides; D054709:Lecithins; D009824:Ointments; D012997:Solvents; D013501:Surface-Active Agents; D016559:Tacrolimus