title: Efficacy of piroxicam plus cisplatin-loaded PLGA nanoparticles in inducing apoptosis in mesothelioma cells.
abstract: OBJECTIVE
  Combined treatment based on cisplatin-loaded Poly(D,L-lactic-co-glicolic)acid (PLGA) nanoparticles (NP-C) plus the NSAID piroxicam was used as novel treatment for mesothelioma to reduce side effects related to cisplatin toxicity.
  
  
  METHODS
  PLGA nanoparticles were prepared by double emulsion solvent evaporation method. Particle size, drug release profile and in vitro cellular uptake were characterized by TEM, DLS, LC/MS and fluorescence microscopy. MSTO-211H cell line was used to analyse NP-C biological efficacy by FACS and protein analysis.
  
  
  RESULTS
  Cisplatin was encapsulated in 197 nm PLGA nanoparticles with 8.2% drug loading efficiency and 47% encapsulation efficiency. Cisplatin delivery from nanoparticles reaches 80% of total encapsulated drug in 14 days following a triphasic trend. PLGA nanoparticles in MSTO-211H cells were localized in the perinuclear space NP-C in combination with piroxicam induced apoptosis using a final cisplatin concentration 1.75 fold less than free drug. Delivered cisplatin cooperated with piroxicam in modulating cell cycle regulators as caspase-3, p53 and p21.
  
  
  CONCLUSIONS
  Cisplatin loaded PLGA nanoparticles plus piroxicam showed a good efficacy in exerting cytotoxic activity and inducing the same molecular apoptotic effects of the free drugs. Sustained cisplatin release allowed to use less amount of drug, decreasing toxic side effects. This novel approach could represent a new strategy for mesothelioma treatment.
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Menale
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Piccolo
authors.forename: Ilaria
authors.initials: I
authors.lastname: Favicchia
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Aruta
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
authors.forename: Carla
authors.initials: C
authors.lastname: Nicolucci
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barba
authors.forename: Damiano Gustavo
authors.initials: DG
authors.lastname: Mita
authors.forename: Stefania
authors.initials: S
authors.lastname: Crispi
authors.forename: Nadia
authors.initials: N
authors.lastname: Diano
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism; D004338:Drug Combinations; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage*; D008654:Mesothelioma / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage* / Q000378:metabolism; D010894:Piroxicam / Q000008:administration & dosage* / Q000378:metabolism; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016896:Treatment Outcome
chemical_list: D004337:Drug Carriers; D004338:Drug Combinations; D010894:Piroxicam; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002945:Cisplatin
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