title: Improved topical delivery of tacrolimus: A novel composite hydrogel formulation for the treatment of psoriasis.
abstract: We have developed a composite hydrogel for improved topical delivery of the poorly soluble drug Tacrolimus (TAC) to psoriasis lesions. TAC is efficiently solubilized in methoxy poly- (ethylene glycol) hexyl substituted poly-(lactic acid) (mPEGhexPLA) based nanocarriers. For convenient and patient-friendly topical administration, TAC loaded polymeric nanocarriers were incorporated in a Carbopol® based hydrogel, to yield a composite hydrogel formulation (TAC composite hydrogel). TAC composite hydrogel was designed to have superior pharmaceutical formulation properties, delivery efficiency and local bioavailability, compared to currently available paraffin-based TAC ointments. Composite hydrogel formulations had good local tolerance and showed no signs of immediate toxicity after repeated topical administration in healthy mice. Skin delivery of TAC composite hydrogel in an imiquimod-induced psoriasis mouse model was found to be twice as high as for the commercial formulation Protopic™, used as benchmark. TAC composite hydrogel showed significant improvement in the in vivo and histopathological features of the imiquimod-induced psoriasis model.
authors.affiliation: Apidel SA, 29 Quai du Mont Blanc, 1201 Geneva, Switzerland. Electronic address: doris00gabriel@gmail.com.
authors.forename: Doris
authors.initials: D
authors.lastname: Gabriel
authors.affiliation: Apidel SA, 29 Quai du Mont Blanc, 1201 Geneva, Switzerland.
authors.forename: Thibault
authors.initials: T
authors.lastname: Mugnier
authors.affiliation: Apidel SA, 29 Quai du Mont Blanc, 1201 Geneva, Switzerland.
authors.forename: Herve
authors.initials: H
authors.lastname: Courthion
authors.affiliation: Biomedcode Hellas SA, 34 Al Fleming Street, 16672 Vari, Athens, Greece.
authors.forename: Ksanthi
authors.initials: K
authors.lastname: Kranidioti
authors.affiliation: Biomedcode Hellas SA, 34 Al Fleming Street, 16672 Vari, Athens, Greece.
authors.forename: Niki
authors.initials: N
authors.lastname: Karagianni
authors.affiliation: Biomedcode Hellas SA, 34 Al Fleming Street, 16672 Vari, Athens, Greece.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Denis
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, CMU-1, Rue Michel Servet, 1211 Geneva 4, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Lapteva
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, CMU-1, Rue Michel Servet, 1211 Geneva 4, Switzerland.
authors.forename: Yogeshvar
authors.initials: Y
authors.lastname: Kalia
authors.affiliation: Apidel SA, 29 Quai du Mont Blanc, 1201 Geneva, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Möller
authors.affiliation: Apidel SA, 29 Quai du Mont Blanc, 1201 Geneva, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Gurny
mesh_terms: D000279:Administration, Cutaneous; D000634:Aminoquinolines; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D020100:Hydrogels; D000077271:Imiquimod; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011108:Polymers / Q000737:chemistry; D011565:Psoriasis / Q000188:drug therapy*; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000634:Aminoquinolines; D004337:Drug Carriers; D020100:Hydrogels; D007166:Immunosuppressive Agents; D011108:Polymers; D000077271:Imiquimod; D016559:Tacrolimus
keywords: Dermatology; Hydrogel; Immune-mediated skin disease; Methoxy poly (ethylen glycol) hexyl-substituted poly (lactic acid); Polymeric nanocarriers; Skin topical drug delivery; Tacrolimus