title: Liposomal voriconazole (VOR) formulation for improved ocular delivery.
abstract: Treating infectious eye diseases topically requires a drug delivery system capable of overcoming the eye's defense mechanisms, which efficiently reduce the drug residence time right after its administration, therefore reducing absorption. In order to try to surpass such administration issues and improve life quality for patients with fungal keratitis, liposomal voriconazol (VOR) formulations were prepared. Formulations were composed of soy phosphatidylcholine (PC) containing or not 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and cholesterol. Liposomes were characterized by their drug entrapment efficiency (EE), drug recovery (DR), average diameter (size) and polydispersivity index (PdI). In vitro mucosal interaction and irritancy levels, ex vivo permeation, as well as the short-term stability were also assessed. Liposomal VOR formulation produced with 7.2:40mM VOR:PC showed to be the most promising formulation: mean size of 116.6±5.9nm, narrow PdI (0.17±0.06), negative zeta potential (∼-7mV) and over 80% of EE and yield, remaining stable for at least 30 days in solution and 90 days after lyophilization. This formulation was classified as 'non-irritant' after HET-CAM's test and was able to deliver about 47.85±5.72μg/cm(2) of VOR into porcine cornea after 30min of permeation test. Such drug levels are higher than the minimal inhibitory concentrations (MIC) of several fungi species isolated from clinical cases of corneal keratitis. Overall results suggest VOR can be effectively incorporated in liposomes for potential topical treatment of fungal keratitis.
authors.affiliation: Laboratory of Food, Drugs and Cosmetics (LTMAC), Faculty of Health Sciences, Universidade de Brasília (UnB), Campus Universitário Darcy Ribeiro, Asa Norte, 70910 900 Brasília, DF, Brazil.
authors.forename: Fernando Augusto Pires
authors.initials: FA
authors.lastname: de Sá
authors.affiliation: Laboratory of Pharmaceutical Technology, School of Pharmacy, Universidade Federal de Goiás (UFG), Rua 240 c/5ª. Avenida, s/n, Setor Leste Universitário, 74605 170 Goiânia, GO, Brazil.
authors.forename: Stephânia Fleury
authors.initials: SF
authors.lastname: Taveira
authors.affiliation: Laboratory of Food, Drugs and Cosmetics (LTMAC), Faculty of Health Sciences, Universidade de Brasília (UnB), Campus Universitário Darcy Ribeiro, Asa Norte, 70910 900 Brasília, DF, Brazil.
authors.forename: Guilherme Martins
authors.initials: GM
authors.lastname: Gelfuso
authors.affiliation: Laboratory of Pharmaceutical Technology, School of Pharmacy, Universidade Federal de Goiás (UFG), Rua 240 c/5ª. Avenida, s/n, Setor Leste Universitário, 74605 170 Goiânia, GO, Brazil.
authors.forename: Eliana Martins
authors.initials: EM
authors.lastname: Lima
authors.affiliation: Laboratory of Food, Drugs and Cosmetics (LTMAC), Faculty of Health Sciences, Universidade de Brasília (UnB), Campus Universitário Darcy Ribeiro, Asa Norte, 70910 900 Brasília, DF, Brazil. Electronic address: tgratieri@gmail.com.
authors.forename: Taís
authors.initials: T
authors.lastname: Gratieri
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry; D002417:Cattle; D002784:Cholesterol / Q000737:chemistry; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D007634:Keratitis / Q000188:drug therapy*; D008081:Liposomes; D046529:Microscopy, Electron, Transmission; D009181:Mycoses / Q000188:drug therapy*; D010713:Phosphatidylcholines / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013552:Swine; D065819:Voriconazole / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D010713:Phosphatidylcholines; D000644:Quaternary Ammonium Compounds; D002784:Cholesterol; D065819:Voriconazole; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane
keywords: Drug delivery; HET-CAM; Liposome; Ocular; Phosphatidylcholine; Voriconazole