Fluorouracil neutrophil extracellular traps formation inhibited by polymer nanoparticle shielding.

Venous thromboembolism is a frequent complication occurring in patients suffering from neoplastic diseases. Since neutrophil extracellular traps (NETs) play an important role both in the development of the tumor growth process and in inducing complications such as thrombosis, indubitably the investigation of the effect of antitumor drugs on the formation of neutrophil extracellular traps and on the ability of such drugs to prevent NETs contribution on carcinogenesis is of great interest. In the present work we studied the effect of 5-fluorouracil (5FU) and its shielded -by amphiphilic poly-N-vinylpyrrolidone (Amph-PVP) nanoparticles-nanoscaled polymeric form on the activation of human neutrophils under ex vivo conditions. Free 5FU at concentrations varying from 0.01 to 10 mg/ml was found to cause a significant (two to three times) and rapid (after 20 min) increase in the total amount of NETs in the blood. Importantly, when 5FU-loaded Amph-PVP nanoparticles were studied under the same conditions, the appearance of NETs in the blood was completely blocked providing strong evidence of their potential as delivery system for 5FU in antitumor therapy.

Preparation and characterization of amphiphilic poly-N-vinylpyrrolidone nanoparticles containing indomethacin.

Amphiphilic poly-N-vinylpyrrolidone derivatives (Amph-PVP) with different molecular weight of hydrophilic PVP fragment and one terminal hydrophobic n-alkyl fragment of different length were synthesized for preparation of nano-scaled particles in aqueous media. To estimate novel polymer efficiency and perspective as basis for drug delivery systems, the polymeric micelle-like particles were prepared by dialysis and solvent evaporation methods. Indomethacin was incorporated into hydrophobic inner core of these nanoparticles as a typical model drug. From the dynamic light-scattering measurements, the size of particles formed was less than 200 nm with narrow monodisperse size distribution and nanoparticles size slightly increased with the amount of indomethacin encapsulated into inner core of Amph-PVP particles. The critical aggregation concentration values for prepared polymer samples determined by fluorescence spectroscopy were in micromole range which is lower than it is for common low molecular weight surfactants. As the hydrophobic fragment of amphiphilic polymer increased, the critical aggregation concentration values decreased. An increase of polymer hydrophilic fragment molecular weight produced larger nanoaggregates. In vitro release experiments using indomethacin-loaded Amph-PVP nanoparticles exhibited the sustained release behavior without any burst effect for most polymer samples.