Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 555, Issue -, Pages 36-48Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2018.11.041
Keywords
Benznidazole; Phase behavior; Rheology; Colloidal systems; Drug delivery system; Chagas disease; Drug targeting
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Funding
- Brazilian National Council for Scientific and Technological Development (CNPq) [483073/2010-5, 481767/2012-6]
- Coordination for the Improvement of Graduate Level (CAPES) [PNPD 23038.007487/2011-91]
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This study explored the transition of lamellar-type liquid crystal (LLC) to biocompatible oil-in-water nanoemulsions able to modify benznidazole (BNZ) release and target the drug to cells infected with the T. cruzi parasite. Three cosolvents (2methylpyrrolidone [NMP], polyethylene glycol [POL], and propylene glycol [PRO] were tested to induce the transition of anisotropic LLC systems to isotropic nanoemulsions. Mixtures of soy phosphatidylcholine with sodium oleate stabilized the dispersions of medium chain triglyceride in water. Rheological measurements, polarized microscopy, and small angle X-ray scattering demonstrated that there is a phase transition from LLC to desired nanoemulsions. These small and narrow droplet-sized nanocarriers exhibited some advantages and promising features, such as the enhanced BNZ aqueous solubility and slow drug release rate. In vitro cell biocompatibility of formulations was assessed in the Vero E6 and SiHa cell lines. Drug-loaded nanoemulsions inhibited the epimastigote growth of the T. cruzi parasite (IC50 0.208 +/- 0.052 mu g mL(-1)) and reduced its infective life form trypomastigote (IC50 0.392 +/- 0.107 mu g mL(-1)). The oil-in-water nanoemulsions were demonstrated as promising biocompatible liquid drug delivery systems capable of improving the BNZ trypanocidal activity for the treatment of Chagas disease.
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