Abstract:
PURPOSE : There is significant interest in the application of nanoparticles to deliver
immunostimulatory signals to cells. We hypothesized that curdlan (immune stimulating
polymer) could be conjugated to PLGA and nanoparticles from this copolymer would
possess immunostimulatory activity, be non-cytotoxic and function as an effective sustained
drug release system.
METHODS : Carbodiimide chemistry was employed to conjugate curdlan to PLGA. The
conjugate (C-PLGA) was characterized using 1H and 13C NMR, FTIR, DSC and TGA.
Nanoparticles were synthesized using an emulsion-solvent evaporation technique.
Immunostimulatory activity was characterized in THP-1 derived macrophages. MTT assay
and real-time impedance measurements were used to characterize polymer and
nanoparticle toxicity and uptake in macrophages. Drug delivery capability was assessed
across Caco-2 cells using rifampicin as a model drug.
RESULTS : Spectral characterization confirmed successful synthesis of C-PLGA. C-PLGA
nanoparticles enhanced phosphorylated ERK production in macrophages indicating cell
stimulation. Nanoparticles provided slow release of rifampicin across Caco-2 cells.
Polymers but not nanoparticles altered the adhesion profiles of the macrophages.
Impedance measurements suggested Ca2+ dependent uptake of nanoparticles by the
macrophages.
CONCLUSIONS : PLGA nanoparticles with macrophage stimulating and sustained drug
delivery capabilities have been prepared. These nanoparticles can be used to stimulate
macrophages and concurrently deliver drug in infectious disease therapy.
