Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 478, Issue 1, Pages 113-123Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2014.11.031
Keywords
Nano-emulsion; PIC emulsification method; PLGA nanoparticles; Cationic dendron; Non-viral gene delivery systems; Antisense therapy
Categories
Funding
- MINECO [CTQ2011-29336-CO3-O1, CTQ2010-20541, CTQ2011-23245]
- Generalitat de Catalunya [2009-SGR-961, 2009-SGR-208]
- Consortium NANO-DENDMED [S2011/BMD-2351]
- CIBER-BBN
- VI National RDI Plan
- IniciativaIngenio
- Consolider Program
- CIBER Actions
- Instituto de Salud Carlos III
- European Regional Development Fund
- AGAUR [FI-DGR 2012]
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The development of novel and efficient delivery systems is often the limiting step in fields such as antisense therapies. In this context, poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles have been obtained by a versatile and simple technology based on nano-emulsion templating and low-energy emulsification methods, performed in mild conditions, providing good size control. O/W polymeric nano-emulsions were prepared by the phase inversion composition method at 25 degrees C using the aqueous solution/polysorbate80/[4 wt% PLGA in ethyl acetate] system. Nano-emulsions formed at oil-to-surfactant (O/S) ratios between 10/90-90/10 and aqueous contents above 70 wt%. Nano-emulsion with 90 wt% of aqueous solution and O/S ratio of 70/30 was chosen for further studies, since they showed the appropriate characteristics to be used as nanoparticle template: hydrodynamic radii lower than 50 nm and enough kinetic stability. Nanoparticles, prepared from nano-emulsions by solvent evaporation, showed spherical shape, sizes about 40 nm, negative surface charges and high stability. The as-prepared nanoparticles were functionalized with carbosilane cationic dendrons through a carbodiimide-mediated reaction achieving positively charged surfaces. Antisense oligonucleotides were electrostatically attached to nanoparticles surface to perform gene-silencing studies. These complexes were non-haemolytic and non-cytotoxic at the concentrations required. The ability of the complexes to impart cellular uptake was also promising. Therefore, these novel nanoparticulate complexes might be considered as potential non-viral carriers in antisense therapy. (C) 2014 Elsevier B.V. All rights reserved.
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