Solid lipid nanoparticles for the delivery of anti-microbial oligonucleotides

González-Paredes, Ana; Sitia, Leopoldo; Ruyra, Àngels; Morris, C J; Wheeler, Grant N.; McArthur, Michael; Gasco, Paolo

doi:10.1016/j.ejpb.2018.11.017

Cited by 50 publications

(36 citation statements)

References 43 publications

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“…However, finding a suitable carrier that offer DNA encapsulation and protection against nucleases with efficient targeting to infection site is a challenge. Gonzalez-Paredes et al [181] investigated the possibility of use of anionic solid lipid nanoparticles that were coated with either the cationic bola amphiphile 12-bis-tetrahydroacridinium or with protamine as a suitable carrier for TFD. Both compounds shifted zeta potential to positive values and demonstrated protective effect of TFD from deoxyribonuclease enzyme and, hence, a preferred accumulation of TFD in bacteria.…”

Section: Anti-microbial Oligonucleotidesmentioning

confidence: 99%

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

et al. 2020

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Based on the recent reports of World Health Organization, increased antibiotic resistance prevalence among bacteria represents the greatest challenge to human health. In addition, the poor solubility, stability, and side effects that lead to inefficiency of the current antibacterial therapy prompted the researchers to explore new innovative strategies to overcome such resilient microbes. Hence, novel antibiotic delivery systems are in high demand. Nanotechnology has attracted considerable interest due to their favored physicochemical properties, drug targeting efficiency, enhanced uptake, and biodistribution. The present review focuses on the recent applications of organic (liposomes, lipid-based nanoparticles, polymeric micelles, and polymeric nanoparticles), and inorganic (silver, silica, magnetic, zinc oxide (ZnO), cobalt, selenium, and cadmium) nanosystems in the domain of antibacterial delivery. We provide a concise description of the characteristics of each system that render it suitable as an antibacterial delivery agent. We also highlight the recent promising innovations used to overcome antibacterial resistance, including the use of lipid polymer nanoparticles, nonlamellar liquid crystalline nanoparticles, anti-microbial oligonucleotides, smart responsive materials, cationic peptides, and natural compounds. We further discuss the applications of antimicrobial photodynamic therapy, combination drug therapy, nano antibiotic strategy, and phage therapy, and their impact on evading antibacterial resistance. Finally, we report on the formulations that made their way towards clinical application.

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Section: Anti-microbial Oligonucleotidesmentioning

confidence: 99%

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

et al. 2020

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“…Furthermore, it is not uncommon to obtain contradictory results in vitro and in vivo, given the large number of biological processes that occur in the body which are difficult to reproduce in vitro. The early developmental vertebrate model Xenopus laevis has been recently proposed as a potential tool, able to bridge the gap between in vitro cell-based assays and mammalian models of toxicity assessment (Webster et al, 2016;Al-Yousuf et al, 2017;Mamusa et al, 2017;Marín-Barba et al, 2018;Saide, Sherwood and Wheeler, 2018;González-Paredes et al, 2019). The mortality, malformations and growth inhibition of Xenopus laevis have been studied, after exposure with metal oxide-based nanomaterials (γ-Fe2O3, TiO2, ZnO and CuO) in a water contamination scenario (Nations, Long, et al, 2011;Nations, Wages, et al, 2011;Bacchetta et al, 2014;Perelshtein et al, 2015).…”

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confidence: 99%

Toxicity and biodegradation of zinc ferrite nanoparticles in Xenopus laevis

et al. 2019

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Zn-doped Fe3O4 magnetic nanoparticles have been proposed as the ideal ferrite for some biomedical applications like magnetic hyperthermia or photothermal therapy because of the possibility to adjust their size and chemical composition in order to design tailored treatments. However, reliable approaches are needed to risk assess Zn ferrite nanoparticles before clinical development. In this work, the in vitro toxicity of the nanoparticles was evaluated in five cellular models (Caco-2, HepG2, MDCK, Calu-3 and Raw 264.7) representing different target organs/systems (gastrointestinal system, liver, kidney, respiratory system and immune system). For the first time, these nanoparticles were evaluated in an in vivo Xenopus laevis model to study whole organism toxicity and their impact on iron and zinc metabolic pathways. Short and long-term in vivo exposure studies provided insights into the contrasting adverse effects between acute and chronic exposure. Quantitative PCR combined with elemental analysis and AC magnetic susceptibility measurements revealed that at short-term exposure (72 h) the nanoparticles' absorption process is predominant, with the consequent over-expression of metal transporters and metal response proteins. At long-term exposure (120 h), there is an up-regulation of 2 metal accumulation involved genes and the return to basal levels of both iron and zinc transporters, involved in the uptake of metals. This suggests that at this stage the nanoparticles' absorption process is residual compared with the following steps in metabolism, distribution and/or excretion processes, indicated by the increase of iron accumulation proteins at both transcriptional and translational level. This testing approach based on a battery of cellular systems and the use of the Xenopus laevis model could be a viable strategy for studying the toxicity, degradability and ultimately the long-term fate of zinc ferrites in the organism.

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“…Both antisense and decoy technologies are currently promising nucleic acid-based strategies for fighting against infectious diseases induced by antibiotic-resistant bacteria, although a main hurdle towards clinical development is still their weak cellular uptake [4,17,51,52]. In addition, our understanding of the role of ssRNA paves the way for using these RNA molecules as potential antibacterial therapeutics, and calling again for the design of an efficient delivery system.…”

Section: Discussionmentioning

confidence: 99%

“…Delivery of ASO in ≥50% of bacteria using LPN is higher than the 14% of E. coli cells transfected by free locked nucleic acids [56], and 30% of transfected cells with solid/lipid nanoparticles [17], but close to DNA delivery in 57% of bacteria, as previously reported with other anionic liposomes [16]. However, the uptake of LPN complexes into bacteria is still inferior to the 70% of E. coli cells positive for DNA after incubation with DNA nanopyramids, although the latter may interact with DNA binding sites on the bacterial membrane [57].…”

Section: Discussionmentioning

confidence: 99%

“…However, the CPP-dependent approach showed several limitations, including the requirement of designing derivatives when resistance to delivery arises from mutations occurring in bacterial transporter proteins [15]. Other strategies involve formulations with anionic liposomes for delivery of ASO [16] and DNA decoy oligonucleotide [17]. A more recent strategy uses lipopolyplexes with ASO being first complexed with polyethylenimine (PEI) before encapsulation of the PEI/ASO polyplex into anionic liposomes, yielding efficient delivery into Gram-negative bacteria [18,19,20,21].…”

Section: Introductionmentioning

confidence: 99%

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Cardiolipin-Based Lipopolyplex Platform for the Delivery of Diverse Nucleic Acids into Gram-Negative Bacteria

et al. 2019

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Antibiotic resistance is a growing public health concern. Because only a few novel classes of antibiotics have been developed in the last 40 years, such as the class of oxazolidinones, new antibacterial strategies are urgently needed (Coates, A.R. et al., 2011). Nucleic acid-based antibiotics are a new type of antimicrobials. However, free nucleic acids cannot spontaneously cross the bacterial cell wall and membrane; consequently, their intracellular delivery into bacteria needs to be assisted. Here, we introduce an original lipopolyplex system named liposome polymer nucleic acid (LPN), capable of versatile nucleic acid delivery into bacteria. We characterized LPN formed with significant therapeutic nucleic acids: 11 nt antisense single-stranded (ss) DNA and double-stranded (ds) DNA of 15 and 95 base pairs (bp), 9 kbp plasmid DNA (pDNA), and 1000 nt ssRNA. All these complexes were efficiently internalized by two different bacterial species, i.e., Escherichia coli and Pseudomonas aeruginosa, as shown by flow cytometry. Consistent with intracellular delivery, LPN prepared with an antisense oligonucleotide and directed against an essential gene, induced specific and important bacterial growth inhibition likely leading to a bactericidal effect. Our findings indicate that LPN is a versatile platform for efficient delivery of diverse nucleic acids into Gram-negative bacteria.

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Solid lipid nanoparticles for the delivery of anti-microbial oligonucleotides

Cited by 50 publications

References 43 publications

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

Toxicity and biodegradation of zinc ferrite nanoparticles in Xenopus laevis

Cardiolipin-Based Lipopolyplex Platform for the Delivery of Diverse Nucleic Acids into Gram-Negative Bacteria

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