title: Design and in vitro evaluation of biocompatible dexamethasone-loaded nanoparticle dispersions, obtained from nano-emulsions, for inhalatory therapy.
abstract: 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°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 (PIC) 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 μg/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 μg/mL. These results allow concluding that these polymeric nanoparticle dispersions are good candidates for inhalatory therapy.
authors.affiliation: Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) and CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), C/Jordi Girona, 18-26, Barcelona 08034, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fornaguera
authors.affiliation: Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) and CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), C/Jordi Girona, 18-26, Barcelona 08034, Spain.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Llinàs
authors.affiliation: Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) and CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), C/Jordi Girona, 18-26, Barcelona 08034, Spain. Electronic address: conxita.solans@iqac.csic.es.
authors.forename: Conxita
authors.initials: C
authors.lastname: Solans
authors.affiliation: Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) and CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), C/Jordi Girona, 18-26, Barcelona 08034, Spain.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Calderó
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004339:Drug Compounding; D065546:Drug Liberation; D004655:Emulsions; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry* / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012138:Respiratory Therapy; D013535:Suspensions; D013552:Swine
chemical_list: D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D004655:Emulsions; D013535:Suspensions; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone
keywords: Dexamethasone; Nano-emulsion; PLGA; Phase inversion composition (PIC) method; Polymeric nanoparticles