Dextrin nanoparticles: Studies on the interaction with murine macrophages and blood clearance

Abstract

The uptake of nanoparticles by cells of the mononuclear phagocytic system limits its use as colloidal drug carriers, reducing the blood circulation time and the ability to reach biological targets. In this work, the interaction between dextrin nanoparticles--recently developed in our laboratory--and murine bone marrow-derived macrophages was evaluated. Cytotoxicity and nitric oxide production were studied, using the MTT assay and the Griess method, respectively. FITC labelled nanoparticles were used to assess the phagocytic uptake and blood clearance after intravenous injection. The phagocytic uptake was analysed in vitro by confocal laser scanning microscopy and fluorescence activated cell sorting. The results show that the nanoparticles are not cytotoxic and do not stimulate the production of nitric oxide by macrophages, in the range of concentrations studied. Nanoparticles are phagocytosed by macrophages and are detected inside the cells, concentrated in cellular organelles. The blood clearance study showed that the blood removal of the nanoparticles occurs with a more pronounced rate in the first 3 h after intravenous administration, with about 30% of the material remaining in systemic circulation at this stage. Given the fairly high blood circulation time and biocompatibility, the dextrin nanoparticles are promising carriers for biomedical applications. Both applications targeting phagocytic, antigen-presenting cells (for vaccination purposes) and different tissues (as drug carriers) may be envisaged, by modulation of the surface properties.

Self-Assembled Dextrin Nanogel as Curcumin Delivery System

“…The colloidal stability of dextrin nanogel (in distilled water or PBS solution) has been previously assessed using dexC 16 with a higher degree of substitution (DS C16 8.7% vs 6.0% in this work), up to 7 days. High stability was observed in both water and PBS solutions, since no aggregates were detected and a low polydispersity index was conserved.…”

“…Dextrin-VA-SC 16 (dexC 16 ) was synthesized as comprehensively described previously [9]. DexC 16 is composed by a hydrophilic dextrin backbone with grafted acrylate groups (VA-vinyl acrylate), which are partially substituted with long alkyl chains (SC 16 ).…”

“…DexC 16 is composed by a hydrophilic dextrin backbone with grafted acrylate groups (VA-vinyl acrylate), which are partially substituted with long alkyl chains (SC 16 ). In this work, dexC 16 with a dextrin degree of substitution, with acrylate groups and alkyl chains of 13.0% (DS VA ) and 6.0% (DS C16 ) respectively, was used. Curcumin was purchased from Fluka and (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) from Promega.…”

“…Nanogel was obtained by dispersion of dexC 16 (lyophilized powder) in water, or phosphate-buffered saline (PBS) solution, under stirring at 50˚C, until a clear solution was obtained. This procedure avoids the use of any organic solvent.…”

“…In order to label nanogel with SAMSA fluorescein (SAMSA-F), the following solutions were prepared: (1) Nanogel solution-10 mg of dexC 16 were dissolved in 1.3 mL of sodium phosphate buffer 0.1 M pH 7 and stirred for 30 min; (2) fluorescein solution-5 mg of SAMSA-F were dissolved in 0.5 mL of NaOH 0.1 M and stirred for 15 min. Afterwards, 7 µL of HCl 6 M and 0.1 mL of NaPO 4 buffer 0.5 M pH 7 were added and stirred for 10 min.…”