期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 125, 期 -, 页码 58-64出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.colsurfb.2014.11.006
关键词
Nano-emulsion; Phase inversion composition (PIC) method; Polymeric nanoparticles; PLGA; Dexamethasone
资金
- MINECO [CTQ2011-29336-CO3-01]
- Generalitat de Catalunya [2009-SGR-961]
- CIBER-BBN for their Research Initiation Fellowship
- AGAUR for their Predoctoral Fellowship [FI-DGR 2012]
Polymeric nanoparticle dispersions containing dexamethasone (DXM) have been prepared from O/W nano-emulsions of the water/polysorbate 80/[4 wt% poly(lactide-co-glycolide) acid + 0.18 wt% DXM in ethyl acetate] system by a low-energy method at 25 degrees C. Nano-emulsions were formed at O/S ratios between 45/55 and 72/25 and water contents above 70 wt% by the phase inversion composition (PLC) method. The mean hydrodynamic diameter of nano-emulsions with a constant water content of 90 wt% and O/S ratios from 50/50 to 70/30 was below 350 nm as assessed by dynamic light scattering. The nanoparticles obtained from these nano-emulsions (by solvent evaporation) showed mean diameters of around 130 nm, as determined by transmission electron microscopy image analysis. Therapeutic concentrations of DXM were encapsulated in the nano-emulsions prior to nanoparticle preparation. DXM entrapment efficiency of the nanoparticle dispersion (above 74 wt%) decreased at increasing O/S ratios of the precursor nano-emulsion while DXM loading, which was around 10 mg/100 mL, showed the reverse tendency. DXM release from nanoparticle dispersions was about an order of magnitude slower than from an aqueous solution. In vitro studies performed in a lung carcinoma cell line and in vitro haemolysis studies performed in red blood cells revealed a dose-dependent toxicity and haemolytic response, respectively. The as-prepared nanoparticle dispersions were non-toxic up to a concentration of 40 mu g/mL and non-haemolytic up to a concentration of 1 mg/mL. After purification, nanoparticle dispersions were non-toxic up to a concentration of 90 mu g/mL. These results allow concluding that these polymeric nanoparticle dispersions are good candidates for inhalatory therapy. (C) 2014 Elsevier B.V. All rights reserved.
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