Application of mPEG-PCL-mPEG Micelles for Anti-Zika Ribavirin Delivery

Abstract

Nanoparticles are rapidly becoming the method of choice for a number of nanomedicine applications, especially drug delivery. Many current nanoparticle models for drug delivery include a metal base with a drug conjugated to its surface. However, this raises concerns regarding toxicity since the conjugated drug and metal-based center of the nanoparticle are generally not biocompatible. A novel approach to solve this dilemma is the development of nanosized biocompatible polymer-based micellar nanoparticles (MNPs), created from methoxy poly(ethylene-glycol) poly(ɛ-caprolactone)-methoxy poly(ethylene glycol) (i.e., mPEG-PCL-mPEG) triblock polymers formed around an antiviral drug of choice, ribavirin. The goal is to create a drug carrier triblock nanoparticle system that is labile at a specific intercellular pH resulting in drug release, leading to the suppression of viral pathogens, and without undue toxicity to the cell. Through this approach we created a drug-loaded nanoparticle that dissociates when exposed to pH of 5.49 (endosomal pH), releasing ribavirin intercellularly, resulting in effective suppression of the mosquito-borne virus, Zika, in JEG-3 cells (gestational choriocarcinoma cells), in comparison to untreated and unencapsulated ribavirin controls as shown by plaque reduction assays and confirmation by RT-PCR. The level of suppression observed by ribavirin-loaded MNPs was achieved while requiring approximately 90% less ribavirin than in experiments utilizing unencapsulated ribavirin. The drug delivery system that is described here has shown significant suppression of Zika virus and suggests a role for this drug delivery system as an antiviral platform against additional viral pathogens.

Keywords: Zika; antiviral; drug delivery; flavivirus; micelle; therapeutic.