title: Encapsulation of dexamethasone into biodegradable polymeric nanoparticles.
abstract: The present paper concerns both the optimization of dexamethasone (DXM) entrapment and its release from biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles prepared by the solvent evaporation process. Since the addition of DXM induced the formation of drug crystals beside the nanoparticle suspension, the influence of several parameters on DXM encapsulation was investigated such as the type of organic solvent and polymer, the DXM initial mass, the evaporation rate of the solvent, the continuous phase saturation and the incorporation of a lipid in the polymer. Nanoparticle size and zeta potential were not modified in the presence of DXM and were respectively around 230 nm and -4 mV. The highest drug loading was obtained using 100 mg PLGA 75:25 in a mixture of acetone-dichloromethane 1:1 (v:v) and 10 mg of DXM. The drug was completely released from this optimized formulation after 4 h of incubation at 37 degrees C. Neither the evaporation rate of the organic solvent, nor the aqueous phase saturation with salt or the incorporation of 1mg 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) within the nanoparticles modified the encapsulation efficiency. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) demonstrated that the drug was molecularly dispersed within the nanoparticles whereas the non-encapsulated DXM crystallized. These results demonstrate the feasibility of encapsulating dexamethasone and its subsequent delivery.
authors.affiliation: Univ Paris Sud, CNRS UMR 8612, School of Pharmacy, 5 Rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gómez-Gaete
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tsapis
authors.forename: Madeleine
authors.initials: M
authors.lastname: Besnard
authors.forename: Amélie
authors.initials: A
authors.lastname: Bochot
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine; D001672:Biocompatible Materials / Q000737:chemistry* / Q000627:therapeutic use; D002152:Calorimetry, Differential Scanning; D003907:Dexamethasone / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D019344:Lactic Acid; D053769:Nanocapsules / Q000737:chemistry* / Q000627:therapeutic use; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry* / Q000627:therapeutic use; D012997:Solvents; D014961:X-Ray Diffraction
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D053769:Nanocapsules; D011108:Polymers; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D015060:1,2-Dipalmitoylphosphatidylcholine; D019344:Lactic Acid; D003907:Dexamethasone