In vitro efficacy of polysaccharide-based nanoparticles containing disease-modifying antirheumatic drugs

Nan Zhang, Patricia R. Wardwell, Rebecca A. Bader

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Purpose: 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.

Original languageEnglish (US)
Pages (from-to)2326-2334
Number of pages9
JournalPharmaceutical Research
Volume31
Issue number9
DOIs
StatePublished - Mar 5 2014

Keywords

  • chitosan
  • drug delivery
  • nanoparticles
  • polysialic acid
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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