title: An elastic liposomal formulation for RNAi-based topical treatment of skin disorders: Proof-of-concept in the treatment of psoriasis.
abstract: RNA interference (RNAi) is a rapidly emerging approach for targeted gene silencing to alleviate disease pathology. However, lack of efficient carriers for targeted delivery delays the clinical translation of RNAi. An interesting target for local RNAi therapeutics is the skin as it allows direct access to target cells. Still, applications are limited due to the effective skin barrier which hinders penetration. Herein, a description is given of a liposomal carrier, called 'DDC642', capable of delivering RNAi molecules to the epidermis of impaired and intact human skin, without targeting the dermis or circulatory system. In a psoriasis tissue model, down-regulation of the psoriasis marker human beta-defensin 2 by DDC642-delivered siRNA was confirmed, providing proof-of-concept. These liposomes thus hold great potential as topical delivery system for RNAi therapeutics in the treatment of numerous skin diseases.
authors.affiliation: Department of Dermatology, Ghent University, Ghent, Belgium. Electronic address: eline.desmet@ugent.be.
authors.forename: Eline
authors.initials: E
authors.lastname: Desmet
authors.affiliation: Department of Dermatology, Ghent University, Ghent, Belgium. Electronic address: stefanie.bracke@ugent.be.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Bracke
authors.affiliation: Department of Pharmaceutics, Ghent University, Ghent, Belgium; Center for Nano and Biophotonics, Ghent University, Ghent, Belgium. Electronic address: katrien.forier@ugent.be.
authors.forename: Katrien
authors.initials: K
authors.lastname: Forier
authors.affiliation: Department of Pharmaceutical Analysis, Ghent University, Ghent, Belgium. Electronic address: lien.taevernier@ugent.be.
authors.forename: Lien
authors.initials: L
authors.lastname: Taevernier
authors.affiliation: Electron microscopy, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands. Electronic address: m.c.a.stuart@rug.nl.
authors.forename: Marc C A
authors.initials: MC
authors.lastname: Stuart
authors.affiliation: Department of Pharmaceutical Analysis, Ghent University, Ghent, Belgium. Electronic address: bart.despiegeleer@ugent.be.
authors.forename: Bart
authors.initials: B
authors.lastname: De Spiegeleer
authors.affiliation: Department of Pharmaceutics, Ghent University, Ghent, Belgium. Electronic address: koen.raemdonck@ugent.be.
authors.forename: Koen
authors.initials: K
authors.lastname: Raemdonck
authors.affiliation: Department of Dermatology, Ghent University, Ghent, Belgium. Electronic address: mireille.vangele@ugent.be.
authors.forename: Mireille
authors.initials: M
authors.lastname: Van Gele
authors.affiliation: Department of Dermatology, Ghent University, Ghent, Belgium. Electronic address: jo.lambert@uzgent.be.
authors.forename: Jo
authors.initials: J
authors.lastname: Lambert
mesh_terms: D000287:Administration, Topical; D002784:Cholesterol / Q000737:chemistry; D004548:Elasticity; D000431:Ethanol / Q000737:chemistry; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D018014:Gene Transfer Techniques; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008081:Liposomes; D008544:Melanocytes / Q000378:metabolism; D035683:MicroRNAs / Q000008:administration & dosage; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011565:Psoriasis / Q000235:genetics / Q000628:therapy*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage; D023083:beta-Defensins / Q000235:genetics
chemical_list: D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D035683:MicroRNAs; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; D034741:RNA, Small Interfering; D023083:beta-Defensins; C094877:dioleoyl phosphatidylethanolamine; D000431:Ethanol; D002784:Cholesterol; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane
keywords: Gene therapy; Lipid-based nanoparticle; Liposome; RNA interference; Skin disorder; Topical drug delivery