Polymer nanoparticle as a delivery system for ribavirin: Do nanoparticle avoid uptake by Red Blood Cells?

Abstract

Ribavirin is an antiviral agent, has a broad-spectrum activity against many RNA and DNA viruses and could be used for treatment of myriad types of viral infections. The conventional therapy of ribavirin is accompanied by dose dependant haemolytic anaemia due to its accumulation into Red Blood Cells (RBCs) that limits its dose, and hence, treatment outcome. It is known from the literature that RBCs have no endocytic mechanisms. Although, recent publications showed some data of nanoparticle (NP) uptake by RBCs, it is still a matter of debate and needs further investigation. In addition, according to our knowledge, No one has tried to quantitate how much NP might be taken up by RBCs and correlate that to the possibility of NP use as a delivery system for ribavirin. This work is a continuation of our previous work trying to figure out the advantages that might be offered by polymer NP to deliver ribavirin to treat viral infections. In this work, we used fluorescently labelled polymer nanoparticle, Rhodamine B isothiocyanate poly (glycerol-adipate) nanoparticle [RBITC-PGA NP] to track and quantitate the amount of NP that might be taken up by RBCs versus Huh7.5, human hepatoma cells as a model of endocytic cells to ascertain the advantages offered by polymer NP to increase safety of ribavirin to improve the treatment outcome of viral infections. Spectro-photofluorometry and flow cytometry showed a negligible amount of NP taken up by RBCs compared to Huh7.5 cells, and therefore, polymer NP could be considered as a promising delivery system for ribavirin and its use could be associated with a better management of viral infections (e.g. Hepatitis C) due to a lower possibility of ribavirin accumulation into RBCs. However, future studies using polymer nanoparticles with a sufficient drug loading and retention of ribavirin will be necessary to confirm these results experimentally and clinically.