In Vitro Efficacy of Polysaccharide-Based Nanoparticles Containing Disease-Modifying Antirheumatic Drugs
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).
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.
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.
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.
KEY WORDSchitosan drug delivery nanoparticles polysialic acid rheumatoid arthritis
Disease-Modifying Antirheumatic Drug
Granulocyte-Macrophage Colony-Stimulating Factor
Acknowledgments AND DISCLOSURES
We thank David Wilson for assistance with the HPLC in evaluating controlled release of DM from the nanoparticles. Cellular uptake of the nanoparticles was observed under the direction of Dr. Martin B. Forstner. This work was supported by NSF grant CBET-1032506.
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