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Int. J. Mol. Sci. 2016, 17(7), 981; doi:10.3390/ijms17070981

Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading

1
Laboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte, UFRN, Gal. Gustavo Cordeiro de Farias, Petrópolis, 59.072-570 Natal, RN, Brazil
2
Department of Chemistry, Federal University of Sergipe, UFS, Alberto Carvalho Campus, Av. Vereador Olímpio Grande, 49.500-000 Itabaiana, SE, Brazil
3
Immunology Laboratory, Department of Clinical Analysis and Toxicology, Federal University of Rio Grande do Norte, UFRN, Gal. Gustavo Cordeiro de Farias, Petrópolis, 59.072-570 Natal, RN, Brazil
*
Author to whom correspondence should be addressed.
Academic Editor: Andreas Taubert
Received: 12 May 2016 / Revised: 13 June 2016 / Accepted: 14 June 2016 / Published: 30 June 2016
(This article belongs to the Section Biomaterial Sciences)
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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. View Full-Text
Keywords: nanoemulsions; liquid crystals; biocompatible colloidal carriers; rheology; lipid-based drug delivery systems; benznidazole nanoemulsions; liquid crystals; biocompatible colloidal carriers; rheology; lipid-based drug delivery systems; benznidazole
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MDPI and ACS Style

Streck, L.; Sarmento, V.H.V.; Machado, P.R.L.; Farias, K.J.S.; Fernandes-Pedrosa, M.F.; da Silva-Júnior, A.A. Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading. Int. J. Mol. Sci. 2016, 17, 981.

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