Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/23340
Title: Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs.
Authors: Larissa Gomes dos Reis
Wing-Hin Lee
Maree Svolos
Lyn Margaret Moir
Rima Jaber
Norbert Windhab
Paul Michael Young
Daniela Traini
Keywords: Aveolar
Bronchial
Autopaghy
Apoptosis
Gene Delivery
Issue Date: 3-Jan-2019
Publisher: Pharmaceutics
Abstract: The use of cell-penetrating peptides (CPPs) in combination with nanoparticles (NPs) shows great potential for intracellular delivery of DNA. Currently, its application is limited due to the potential toxicity and unknown long-term side effects. In this study NPs prepared using a biodegradable polymer, poly(lactic–co–glycolic acid (PLGA) in association with a CPP, was assessed on two lung epithelial cell lines (adenocarcinomic human alveolar basal epithelial cells (A549) and normal bronchial epithelial cells (Beas-2B cells)). Addition of CPP was essential for intracellular internalization. No effects were observed on the mitochondrial activity and membrane integrity. CellsexposedtotheNPs–DNA–CPPshowedlowinflammatoryresponse,lowlevelsofapoptosisand no activation of caspase-3. Increase in necrotic cells (between 10%–15%) after 24 h of incubation and increase in autophagy, induced by NPs–DNA–CPP, are likely to be related to the lysosomal escape mechanism. Although oxidative stress is one of the main toxic mechanisms of NPs, NPs–DNA–CPP showed decreased reactive oxygen species (ROS) production on Beas-2B cells, with potential antioxidant effect of CPP and no effect on A549 cells. This NP system appears to be safe for intracellular delivery of plasmid DNA to the lung epithelial cells. Further investigations should be conducted in other lung-related systems to better understand its potential effects on the lungs
URI: 10.3390/pharmaceutics11010012
http://ir.unikl.edu.my/jspui/handle/123456789/23340
ISSN: 1999-4923
Appears in Collections:Journal Articles



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.