title: Nimesulide-loaded nanoparticles for the potential coadjuvant treatment of prostate cancer.
abstract: Nimesulide (NS)-loaded nanoparticles (NPNS) were prepared from polylactide-co-glycolide (PLGA) and eventually coated with chitosan (NPNSCS). Nanoparticles (NP) were spherical with sizes 379 ± 59 nm for NPNS and 393 ± 66 nm for NPNSCS and zeta potentials of -15 ± 3 mV for NPNS to 10 ± 4 mV for NPNSCS, suggesting an efficient coating. Drug encapsulation rate was high (88 ± 5% and 83 ± 7% of added drug) for NPNS and NPNSCS, respectively. After NP washing and re-suspension, 98 ± 2% and 99 ± 1% of the drug initially entrapped remained associated to NP. NS was dispersed in amorphous state within the polymeric matrix. Two-fold dilution of NP with pH 7.4 PBS provoked no drug release. However, 30-40% NS was released after a 1/10 dilution. NPNSCS and NPNS diluted 1/100 reduced the encapsulated drug to around 30% and 70%, respectively. In contrast, 100% NS was released from NP under sink conditions in less than 2h. The permeability of free-NS (1-1.5 × 10(-5)cm/s) was compared with NPNS (NPNS = 6.4-8.1 × 10(-6)cm/s and NPNSCS = 5.5-7.0 × 10(-6)cm/s) using the PAMPA assay. The cytotoxicity of free-NS and NS in NP on model prostate cancer cells PC-3 and DU-145 showed the highest cytotoxic effect with NPNSCS on PC-3 cells (IC50 = 89 μM).
authors.affiliation: Unit of Pharmacy and Pharmaceutical Technology, Department of Biomedical Sciences, School of Pharmacy, Ctra A-2km 33.600, University Campus, University of Alcalá, 28871 Alcalá de Henares, Madrid, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Huerta
authors.affiliation: Unit of Pharmacy and Pharmaceutical Technology, Department of Biomedical Sciences, School of Pharmacy, Ctra A-2km 33.600, University Campus, University of Alcalá, 28871 Alcalá de Henares, Madrid, Spain.
authors.forename: María del Rosario
authors.initials: Mdel R
authors.lastname: Aberturas
authors.affiliation: Unit of Pharmacy and Pharmaceutical Technology, Department of Biomedical Sciences, School of Pharmacy, Ctra A-2km 33.600, University Campus, University of Alcalá, 28871 Alcalá de Henares, Madrid, Spain. Electronic address: jesus.molpeceres@uah.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Molpeceres
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002470:Cell Survival; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011471:Prostatic Neoplasms / Q000188:drug therapy; D017550:Spectroscopy, Fourier Transform Infrared; D013449:Sulfonamides / Q000008:administration & dosage*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D013449:Sulfonamides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan; C012655:nimesulide
keywords: Nimesulide; PAMPA; PLGA; chitosan; nanoparticles; prostate cancer