Preparation, characterization and in vitro antiviral activity evaluation of foscarnet-chitosan nanoparticles

• A new nanoparticulate system for foscarnet delivery was prepared and characterized.
• Nanoparticles were obtained by ionotropic gelation of chitosan induced by foscarnet.
• Nanoparticles were also further crosslinked by glutaraldehyde.
• The stability of this system in phosphate buffer saline was determined.
• Its in vitro antiviral activity against infected lung fibroblasts cells was investigated.

A new nanoparticulate system for foscarnet delivery was prepared and evaluated. Nanoparticles were obtained by ionotropic gelation of chitosan induced by foscarnet itself, acting as an ionotropic agent in a manner similar to tripolyphosphate anion. A Doehlert design allowed finding the suitable experimental conditions. Nanoparticles were between 200 and 300 nm in diameter (around 450 nm after redispersion). Nanoparticle size increased after 5 h, but no size increase was observed after 48 h when nanoparticles were crosslinked with glutaraldehyde. Zeta potential values of noncrosslinked and crosslinked nanoparticles were between 20 and 25 mV, while drug loading of noncrosslinked nanoparticles was about 40% w/w (55% w/w for crosslinked nanoparticles). Nanoparticle yield was around 25% w/w. Crosslinked nanoparticles showed a controlled drug release. Foscarnet released from nanoparticles maintained the antiviral activity of the free drug when tested in vitro against lung fibroblasts (HELF) cells infected with HCMV strain AD-169. Moreover, nanoparticles showed no toxicity on non-infected HELF cells. These nanoparticles may represent a delivery system that could improve the therapeutic effect of foscarnet.

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