title: Penetration and biological effects of topically applied cyclosporin A nanoparticles in a human skin organ culture inflammatory model.
abstract: Systemic antipsoriatic therapies have potentially life-threatening, long-term side effects. The efficacy of topical drugs is poor, but may be improved by the use of delivery systems based on drug nanoparticles. To produce nanoparticles (NP) composed of cyclosporin A, a classical antipsoriatic drug, and to investigate their penetration and biological effects in human skin affected by psoriatic symptoms, poly-ε-caprolactone (PCL) and cyclosporin A (CsA) NP were prepared by the solvent evaporation method. Skin penetration was followed using fluorescently labeled NP in human skin organ cultures (hSOC). Psoriatic symptoms were mimicked in hSOC by the treatment with epidermal growth factor (EGF) and bacterial lipopolysaccharide (LPS). Cell viability in hSOC was evaluated by the resazurin test, and cytokine secretion into the growth medium was measured by immunodetection. We showed that topically applied NP diffused throughout the epidermis within two hours and through the dermis within the following day. They significantly reduced the secretion of inflammatory cytokines IL-1β, IL-6, IL-8, IL-20 and IL-23. At active doses, no cytotoxicity was detected. This type of NP display relevant properties for the use as topical anti-inflammatory agents and may help to resorb psoriatic lesions.
authors.affiliation: Department of Biological Chemistry, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Frušić-Zlotkin
authors.forename: Yoram
authors.initials: Y
authors.lastname: Soroka
authors.forename: Ran
authors.initials: R
authors.lastname: Tivony
authors.forename: Liraz
authors.initials: L
authors.lastname: Larush
authors.forename: Lilian
authors.initials: L
authors.lastname: Verkhovsky
authors.forename: François Menahem
authors.initials: FM
authors.lastname: Brégégère
authors.forename: Rami
authors.initials: R
authors.lastname: Neuman
authors.forename: Shlomo
authors.initials: S
authors.lastname: Magdassi
authors.forename: Yoram
authors.initials: Y
authors.lastname: Milner
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000493:pharmacokinetics*; D016207:Cytokines / Q000378:metabolism; D003872:Dermatitis / Q000188:drug therapy* / Q000378:metabolism; D003879:Dermatologic Agents / Q000493:pharmacokinetics*; D004655:Emulsions / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D053758:Nanoparticles; D009924:Organ Culture Techniques; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D003879:Dermatologic Agents; D004655:Emulsions; D016572:Cyclosporine