title: In vitro efficacy of polysaccharide-based nanoparticles containing disease-modifying antirheumatic drugs.
abstract: OBJECTIVE
  To evaluate the therapeutic efficacy of dexamethasone (DM) and methotrexate (MTX) entrapped within polysialic acid (PSA)-trimethyl chitosan (TMC) nanoparticles using an in vitro model of rheumatoid arthritis (RA).
  
  
  METHODS
  The loading capacity of the PSA-TMC nanoparticles was determined. An RA in vitro model was developed by stimulating a synovial cell line with a proinflammatory mediator. Multiplex immunoassay was used to determine changes in the secretion of interleukin-6 (IL-6), interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF) by the in vitro model following administration of the DM- and MTX-loaded nanoparticles.
  
  
  RESULTS
  The loading capacity of the PSA-TMC nanoparticles was approximately 0.1 mg of drug/mg of nanoparticle. When applied to our in vitro model of RA, there were no significant differences in the concentrations of IL-6 and IL-8 when comparing the free drugs and drug-loaded nanoparticles, administered at concentration of 0.1 mg/ml and 1.0 mg/ml, respectively.
  
  
  CONCLUSIONS
  The present study verified that MTX and DM are able to retain bioactivity when loaded into PSA-TMC nanoparticles. Although in vitro efficacy was not increased, the in vivo efficacy will likely be enhanced by the site-specific targeting conferred by nanoparticle entrapment.
authors.affiliation: Syracuse Biomaterials Institute Department of Biomedical and Chemical Engineering, Syracuse University, 318 Bowne Hall, Syracuse, New York, 13244, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Wardwell
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Bader
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002460:Cell Line; D048271:Chitosan / Q000031:analogs & derivatives; D003907:Dexamethasone / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D008727:Methotrexate / Q000008:administration & dosage* / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D012794:Sialic Acids / Q000737:chemistry; D013583:Synovial Membrane / Q000166:cytology
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D004337:Drug Carriers; D015850:Interleukin-6; D016209:Interleukin-8; D012794:Sialic Acids; C021319:polysialic acid; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D048271:Chitosan; D008727:Methotrexate