title: Formulation and ex vivo evaluation of polymeric nanoparticles for controlled delivery of corticosteroids to the skin and the corneal epithelium.
abstract: Controlled delivery of corticosteroids using nanoparticles to the skin and corneal epithelium may reduce their side effects and maximize treatment effectiveness. Dexamethasone-loaded ethyl cellulose, Eudragit® RS and ethyl cellulose/Eudragit® RS nanoparticles were prepared by the solvent evaporation method. Dexamethasone release from the polymeric nanoparticles was investigated in vitro using Franz diffusion cells. Drug penetration was also assessed ex vivo using excised human skin. Nanoparticle toxicity was determined by MTT and H2DCFDA assays. Eudragit® RS nanoparticles were smaller and positively charged but had a lower dexamethasone loading capacity (0.3-0.7%) than ethyl cellulose nanoparticles (1.4-2.2%). By blending the two polymers (1:1), small (105nm), positively charged (+37mV) nanoparticles with sufficient dexamethasone loading (1.3%) were obtained. Dexamethasone release and penetration significantly decreased with decreasing drug to polymer ratio and increased when Eudragit® RS was blended with ethyl cellulose. Ex vivo, drug release and penetration from the nanoparticles was slower than a conventional cream. The nanoparticles bear no toxicity potentials except ethyl cellulose nanoparticles had ROS generation potential at high concentration. In conclusion, the nanoparticles showed great potential to control the release and penetration of corticosteroids on the skin and mucus membrane and maximize treatment effectiveness.
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Balzus
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
authors.forename: Fitsum Feleke
authors.initials: FF
authors.lastname: Sahle
authors.affiliation: Institute for Pharmacy, Pharmacology and Toxicology, Freie Universität Berlin, Königin-Luise-Str. 2-4, 14195 Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hönzke
authors.affiliation: Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gerecke
authors.affiliation: Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany; Department of Molecular Biology, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Schumacher
authors.affiliation: Institute for Pharmacy, Pharmacology and Toxicology, Freie Universität Berlin, Königin-Luise-Str. 2-4, 14195 Berlin, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hedtrich
authors.affiliation: Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kleuser
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany. Electronic address: bodmeier@zedat.fu-berlin.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Bodmeier
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000305:Adrenal Cortex Hormones / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003907:Dexamethasone / Q000737:chemistry; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation / Q000502:physiology; D019573:Epithelium, Corneal / Q000187:drug effects*; D005260:Female; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012867:Skin / Q000187:drug effects*; D012995:Solubility
chemical_list: D000180:Acrylic Resins; D000305:Adrenal Cortex Hormones; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; C050528:Eudragit RS; D003907:Dexamethasone; C013517:ethyl cellulose; D002482:Cellulose
keywords: Dermal delivery; Dexamethasone; Ethyl cellulose; Eudragit® RS; Ocular delivery; Polymeric nanoparticle