Preparation and Characterization of PLGA Nanoparticles Containing Plasmid DNA Encoding Human IFN-lambda-1/IL-29

摘要

During the 15 years since the discovery of type III human interferons [IFN-λ1(IL-29), IFN-λ2(IL-28A), and IFN-λ3(IL-28B)], numerous biological properties such as anticancer, antiviral, and immunomodulatory activities of this new IFN family have been investigated. Several studies have shown that the encapsulation of pcDNA with PLGA nanoparticles (NPs) protects them against DNase enzyme action and increases the efficiency of gene delivery to the cells. The purpose of this study was to encapsulate pcDNA encoding IFN-λ1 (pIFN-λ1) with a simple and cost-effective method using PLGA NPs. The pIFN-λ1-loaded PLGA NPs were produced by a double-emulsion-solvent evaporation method and characterized in terms of size, size distribution, and zeta potential by DLS and morphologically by SEM and TEM. The bioactivity of NPs was also examined by fluorescent microscopy. The results showed that IFN-λ1 expressed by HEK293T cells could protect HepC-2 cells from the cytopathic effects of EMCV. The NPs were spherical in shape with a mean diameter of 380 ± 3 nm, a zeta potential of −3.3 ± 7.6 mV, an encapsulation efficiency of 75 ± 5%, and a loading capacity of 0.83 ± 0.06. The NPs were also bioactive and easily engulfed by RAW264.7 cells. The pIFN-λ1 could be sustainably released from NPs. Due to the facility and affordability of encapsulation of pIFN-λ1 in the PLGA NPs proposed in this study and the advantages of encapsulation by PLGA, it appeared rational to use pIFN-λ1-loaded NPs instead of naked pIFN-λ1 to determine other unexplained activities of this new cytokine or to use it as an alternative or adjunct to current IFN-α therapy.