Microfluidic-assisted nanoprecipitation of antiviral-loaded polymeric nanoparticles

Abstract

The chemical treatment called “chemotherapy of plants” consists in the in vivo administration of substances able to interfere with viral replication. The current availability of synthetic molecules with a high chemotherapeutic index, i.e. with a high ratio between the maximum concentration tolerated and the minimum effective, together with the possibility to further widen the therapeutic window by the use of appropriate nanocarriers, seems to open on the application level of a novel chemical approach to treat plant viral infections. Ribavirin, for example, is a synthetic water-soluble nucleoside that possesses broad spectrum activity against a variety of DNA and RNA plant viruses. As well known, water-soluble drugs are generally difficult to encapsulate in solid particles. Chemical modification of these drugs, such as esterification, may increase their encapsulation efficiency, but may also decrease bioactivity. In this work we have synthesized stable solid monodispersed PLGA (poly-d,l-lactic-co-glycolic acid) NPs with diameters ranging from 50 to 200nm containing ribavirin by using a microfluidic reactor with a flow-focusing geometry. Previous work carried out in our lab showed an improvement of drug loading efficiency when using a microfluidic approach in comparison with traditional nanoprecipitation methods for nanoencapsulation. On this basis we optimized Ribavirin loading within PLGA NPs by investigating the influence of different operating conditions, such as polymer concentration, flow rate ratio, τmix, microreactor-focusing channel diameter and length, on nanoparticle size and morphology. NPs characterization was performed by Dynamic light scattering (DLS) measurements and by scanning electron microscopy (SEM). The synthesized NPs showed a significant drug loading efficiency.