Preparation and characterization of foscarnet/chitosan nanoparticles

Purpose: Foscarnet is an antiviral agent which inhibits the activity of herpesvirus DNA polymerase, including herpes simplex virus types 1 and 2, varicella zoster, cytomegalovirus, human immunodeficiency virus (HIV) and other viruses. A major problem associated with the administration of Foscarnet is its marked toxicity. The encapsulation of the drug into chitosan nanoparticles can be an interesting approach to reduce the toxic effects of this drug. The main goal of the present work was to create a type of nanoparticles in which the drug itself is a structural component of the system. Methods: Nanoparticles with a positive surface charge were prepared through the electrostatic interaction of chitosan with Foscarnet in acidic solution. A Doehlert design for two variables was used to study the effect of the drug/polymer ratio, at a fixed solution volume, on nanoparticle properties. Selected samples were subjected to centrifugation (11000 x g for 2 h, T= 10 °C) and the residue was lyophilized and weighed to determine the yield and the drug loading. Results: Nanoparticles showed a mean particle diameter of 304±4 nm. The encapsulation efficiency was 69% w/w. Drug loading of nanoparticles, which had a zeta potential of 15.2±0.4 mV, was equal to 46% w/w and the particle yield was around 35% w/w. Nanoparticles showed a good stability after redispersion in water for at least 15 days. Conclusions: Foscarnet, acting in a manner similar to sodium tripolyphosphate, induced chitosan gelation and allowed to obtain positively charged nanoparticles, with small size and high zeta potential. This result was achieved trough a proper selection of the drug/polymer ratio. It is likely that these nanoparticles could allow a higher uptake of the drug into infected cells, as well as an absorption increase by mucosal epithelium thereby also making the oral route more effective for the administration of Foscarnet.