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

ABSTRACT: During the 15 years since the discovery of type III human interferons [IFN-?1(IL-29), IFN-?2(IL-28A), and IFN-?3(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-?1 (pIFN-?1) with a simple and cost-effective method using PLGA NPs. The pIFN-?1-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-?1 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-?1 could be sustainably released from NPs. Due to the facility and affordability of encapsulation of pIFN-?1 in the PLGA NPs proposed in this study and the advantages of encapsulation by PLGA, it appeared rational to use pIFN-?1-loaded NPs instead of naked pIFN-?1 to determine other unexplained activities of this new cytokine or to use it as an alternative or adjunct to current IFN-? therapy.

SUBMITTER: Amir Kalvanagh P

PROVIDER: S-EPMC6487415 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Amir Kalvanagh Parisa P Ebtekara Masoumeh M Kokhaei Parviz P Soleimanjahi Hoorieh H

Iranian journal of pharmaceutical research : IJPR 20190101 1

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 ...[more]

PMID: 31089352

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Project description:The encapsulation of peptides and proteins in nanosystems has been extensively investigated for masking unfavorable biopharmaceutical properties, including short half-life and poor permeation through biological membranes. Therefore, the aim of this work was to encapsulate a small antimicrobial hydrophilic peptide (H-Ser-Pro-Trp-Thr-NH2, FS10) in PEG-PLGA (polyethylene glycol-poly lactic acid-co-glycolic acid) nanoparticles (Nps) and thereby overcome the common limitations of hydrophilic drugs, which because they facilitate water absorption suffer from rapid degradation. FS10 is structurally related to the well-known RNAIII inhibiting peptide (RIP) and inhibits S. aureus biofilm formation. Various parameters, including different method (double emulsion and nanoprecipitation), pH of the aqueous phase and polymeric composition, were investigated to load FS10 into PEG-PLGA nanoparticles. The combination of different strategies resulted in an encapsulation efficiency of around 25% for both the double emulsion and the nanoprecipitation method. It was found that the most influential parameters were the pH-which tailors the peptides charge-and the polymeric composition. FS10-PEG-PLGA nanoparticles, obtained under optimized parameters, showed size lower than 180 nm with zeta potential values ranging from -11 to -21 mV. In vitro release studies showed that the Nps had an initial burst release of 48-63%, followed by a continuous drug release up to 21 h, probably caused by the porous character of the Nps. Furthermore, transmission electron microscopy (TEM) analysis revealed particles with a spherical morphology and size of around 100 nm. Antimicrobial assay showed that the minimum inhibitory concentration (MIC) of the FS10-loaded Nps, against S. aureus strains, was lower (>128 µg/mL) than that of the free FS10 (>256 µg/mL). The main goal of this work was to develop polymeric drug delivery systems aiming at protecting the peptide from a fast degradation, thus improving its accumulation in the target site and increasing the drug-bacterial membrane interactions.

Dataset Information

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

Publications

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

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