title: Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading.
abstract: Previous studies reported low benznidazole (BNZ) loading in conventional emulsions due to the weak interaction of the drug with the most common oils used to produce foods or pharmaceuticals. In this study, we focused on how the type of surfactant, surfactant-to-oil ratio w/w (SOR) and oil-to-water ratio w/w (OWR) change the phase behavior of different lipid-based drug delivery systems (LBDDS) produced by emulsion phase inversion. The surfactant mixture composed of soy phosphatidylcholine and sodium oleate (1:7, w/w, hydrophilic lipophilic balance = 16) stabilized medium chain triglyceride in water. Ten formulations with the clear aspect or less turbid dispersions (five with the SOR ranging from 0.5 to 2.5 and five with the OWR from 0.06 to 0.4) were selected from the phase behavior diagram to assess structural features and drug-loading capacity. The rise in the SOR induced the formation of distinct lipid-based drug delivery systems (nanoemulsions and liquid crystal lamellar type) that were identified using rheological measurements and cross-polarized light microscopy images. Clear dispersions of small and narrow droplet-sized liquid-like nanoemulsions, Newtonian flow-type, were produced at SOR from 0.5 to 1.5 and OWR from 0.12 to 0.4, while clear liquid or gel-like liquid crystals were produced at SOR from 1.5 to 2.5. The BNZ loading was improved according to the composition and type of LBDDS produced, suggesting possible drug location among surfactant layers. The cell viability assays proved the biocompatibility for all of the prepared nanoemulsions at SOR less than 1.5 and liquid crystals at SOR less than 2.5, demonstrating their promising features for the oral or parenteral colloidal delivery systems containing benznidazole for Chagas disease treatment.
authors.affiliation: Laboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte, UFRN, Gal. Gustavo Cordeiro de Farias, Petr&#243;polis, 59.072-570 Natal, RN, Brazil. leticiastreck@gmail.com.
authors.forename: Letícia
authors.initials: L
authors.lastname: Streck
authors.affiliation: Department of Chemistry, Federal University of Sergipe, UFS, Alberto Carvalho Campus, Av. Vereador Ol&#237;mpio Grande, 49.500-000 Itabaiana, SE, Brazil. vhsarmento@gmail.com.
authors.forename: Víctor H V
authors.initials: VH
authors.lastname: Sarmento
authors.affiliation: Immunology Laboratory, Department of Clinical Analysis and Toxicology, Federal University of Rio Grande do Norte, UFRN, Gal. Gustavo Cordeiro de Farias, Petr&#243;polis, 59.072-570 Natal, RN, Brazil. paulamachado2@hotmail.com.
authors.forename: Paula R L
authors.initials: PR
authors.lastname: Machado
authors.affiliation: Immunology Laboratory, Department of Clinical Analysis and Toxicology, Federal University of Rio Grande do Norte, UFRN, Gal. Gustavo Cordeiro de Farias, Petr&#243;polis, 59.072-570 Natal, RN, Brazil. kfarias3@hotmail.com.
authors.forename: Kleber J S
authors.initials: KJ
authors.lastname: Farias
authors.affiliation: Laboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte, UFRN, Gal. Gustavo Cordeiro de Farias, Petr&#243;polis, 59.072-570 Natal, RN, Brazil. mpedrosa@ufrnet.br.
authors.forename: Matheus F
authors.initials: MF
authors.lastname: Fernandes-Pedrosa
authors.affiliation: Laboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte, UFRN, Gal. Gustavo Cordeiro de Farias, Petr&#243;polis, 59.072-570 Natal, RN, Brazil. arnobiosilva@ufrnet.br.
authors.forename: Arnóbio Antônio
authors.initials: AA
authors.lastname: da Silva-Júnior
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D000067493:Dynamic Light Scattering; D004655:Emulsions / Q000737:chemistry; D050866:Liquid Crystals / Q000737:chemistry; D008853:Microscopy; D049329:Nanostructures / Q000737:chemistry; D009593:Nitroimidazoles / Q000737:chemistry* / Q000633:toxicity; D009821:Oils / Q000737:chemistry; D044367:Phase Transition; D012212:Rheology; D013501:Surface-Active Agents / Q000737:chemistry; D014709:Vero Cells; D014867:Water / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D004655:Emulsions; D009593:Nitroimidazoles; D009821:Oils; D013501:Surface-Active Agents; D014867:Water; C009999:benzonidazole
keywords: benznidazole; biocompatible colloidal carriers; lipid-based drug delivery systems; liquid crystals; nanoemulsions; rheology