Solid lipid nanoparticles for the delivery of anti-microbial oligonucleotides

Gonzalez-Paredes, Ana, Sitia, Leopoldo, Ruyra, Angels, Morris, Christopher ORCID:, Wheeler, Grant N. ORCID:, McArthur, Michael and Gasco, Paolo (2019) Solid lipid nanoparticles for the delivery of anti-microbial oligonucleotides. European Journal of Pharmaceutics and Biopharmaceutics, 134. pp. 166-177. ISSN 0939-6411

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Novel alternatives to antibiotics are urgently needed for the successful treatment of antimicrobial resistant (AMR) infections. Experimental antibacterial oligonucleotide therapeutics, such as transcription factor decoys (TFD), are a promising approach to circumvent AMR. However, the therapeutic potential of TFD is contingent upon the development of carriers that afford efficient DNA protection against nucleases and delivery of DNA to the target infection site. As a carrier for TFD, here we present three prototypes of anionic solid lipid nanoparticles that were coated with either the cationic bolaamphiphile 12-bistetrahydroacridinium or with protamine. Both compounds switched particles zeta potential to positive values, showing efficient complexation with TFD and demonstrable protection from deoxyribonuclease. The effective delivery of TFD into bacteria was confirmed by confocal microscopy while SLN-bacteria interactions were studied by flow cytometry. Antibacterial efficacy was confirmed using a model TFD targeting the Fur iron uptake pathway in E.coli under microaerobic conditions. Biocompatibility of TFDSLN was assessed using in vitro epithelial cell and in vivo Xenopus laevis embryo models. Taken together these results indicate that TFD-SLN complex can offer preferential accumulation of TFD in bacteria and represent a promising class of carriers for this experimental approach to tackling the worldwide AMR crisis.

Item Type: Article
Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: LivePure Connector
Date Deposited: 21 Nov 2018 14:30
Last Modified: 21 Oct 2022 20:34
DOI: 10.1016/j.ejpb.2018.11.017

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