Bacterial lipase triggers the release of antibiotics from digestible liquid crystal nanoparticles

Thorn, Chelsea R.; Clulow, Andrew J.; Boyd, Ben J.; Prestidge, Clive A.; Thomas, Nicky

doi:10.1016/j.jconrel.2019.12.037

Cited by 43 publications

(36 citation statements)

References 80 publications

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“…Previously, MO‐ and PHY‐LCNPs containing no drug and small molecule hydrophilic antibiotics (i.e., CIP) had an inverse hexagonal liquid crystal phase structure that upon dilution (i.e., in media for release and activity assessment), switched to the bicontinuous cubic phase structure. [ 25 ] The structural unit of the TOB LCNPs is equivalent due to antibiotics molecular size and hydrophilicity and is structurally demonstrated in the schematic in Figure 1D. In comparison, the simplistic structure of the liposomes is shown schematically in Figure 1E.…”

Section: Resultsmentioning

confidence: 99%

“…TOB was released rapidly from the LCNPs within 2 h, in line with our previous reports on CIP‐loaded LCNPs. [ 25 ] The rate of TOB released from the MO‐LCNPs was initially higher compared to PHY‐LCNPs; however, it became equivalent after the plateau. According to Higuchi, [ 31 ] the lipid liquid crystal matrix structure controls the release of the loaded antibiotics by diffusion.…”

Section: Resultsmentioning

confidence: 99%

“…As aforementioned, the CIP MO‐LCNPs were previously characterized and demonstrated a similar release profile to TOB. [ 25 ] Over a range of concentrations, the antimicrobial effect of CIP in the simplified PAO1 biofilm model did not alter after loading in LCNPs, nor in the physical mixture of CIP with drug‐free LCNPs (Figure 2B), that is, CIP's activity was unable to be further decreased beyond 10 000 CFU mL −1 .…”

Section: Resultsmentioning

confidence: 99%

“…LCNPs were formed with MO (Myverol 18–99 K (part number: 5D01253, Kerry Ingredients, and Flavours Egham, Surrey, UK) or PHY (DSM Heerlen, the Netherlands), via the hydrotrope dilution method. [ 25 ] MO or PHY (100 mg), Pluronic F‐127 (15 mg, Sigma‐Aldrich, Castle Hill, NSW, Australia), and propylene glycol (0.26 g, Sigma‐Aldrich, Castle Hill, NSW, Australia) were mixed by vortexing for 2 min and then completely dissolved in 10 mL chloroform (high‐performance liquid chromatography (HPLC) grade, 1% ethanol, ChemSupply, Port Adelaide, SA, Australia) in glass scintillation vials. A stream of nitrogen gas evaporated the chloroform, leaving behind a thick lipid film on the inside walls of the flask.…”

Section: Methodsmentioning

confidence: 99%

“…As previously described, pressure ultrafiltration stirred cell (Amicon, Merck Millipore, Bayswater, VIC, Australia) indirectly determines the total amount of TOB loaded in the LCNPs and liposomes. [ 25 ] 2.5 mL of the LCNPs suspensions (undiluted) was transferred into the cell containing a pre‐soaked ultrafiltration disc made of biomax polyethersulfone, 500 kDa NMWL (Merck Millipore, Bayswater, VIC, Australia). Upon applying 100 kPa of nitrogen gas, the LCNPs were subjected to ultrafiltration that produces a filtrate that was free of the LCNPs due to the particle size restriction of the ultrafiltration disc.…”

Section: Methodsmentioning

confidence: 99%

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Tobramycin Liquid Crystal Nanoparticles Eradicate Cystic Fibrosis‐Related Pseudomonas aeruginosa Biofilms

Thorn

Carvalho-Wodarz

Horstmann

et al. 2021

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Pseudomonas aeruginosa biofilms cause persistent and chronic infections, most known clinically in cystic fibrosis (CF). Tobramycin (TOB) is a standard anti‐pseudomonal antibiotic; however, in biofilm infections, its efficacy severely decreases due to limited permeability across the biofilm matrix. Herewith, a biomimetic, nanostructured, lipid liquid crystal nanoparticle‐(LCNP)‐formulation is discovered to significantly enhance the efficacy of TOB and eradicate P. aeruginosa biofilm infections. Using an advanced, biologically‐relevant co‐culture model of human CF bronchial epithelial cells infected with P. aeruginosa biofilms at an air–liquid interface, nebulized TOB‐LCNPs completely eradicated 1 × 109 CFU mL−1 of P. aeruginosa after two doses, a 100‐fold improvement over the unformulated antibiotic. The enhanced activity of TOB is not observed with a liposomal formulation of TOB or with ciprofloxacin, an antibiotic that readily penetrates biofilms. It is demonstrated that the unique nanostructure of the LCNPs drives the enhanced penetration of TOB across the biofilm barrier, but not through the healthy lung epithelium barrier, significantly increasing the available antibiotic concentration at the site of infection. The LCNPs are an innovative strategy to improve the performance of TOB as a directed pulmonary therapy, enabling the administration of lower doses, reducing the toxicity, and amplifying the anti‐biofilm activity of the anti‐pseudomonal antibiotic.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Tobramycin Liquid Crystal Nanoparticles Eradicate Cystic Fibrosis‐Related Pseudomonas aeruginosa Biofilms

Thorn

Carvalho-Wodarz

Horstmann

et al. 2021

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Colloidal Structure Dictates Antimicrobial Efficacy in LL‐37 Self‐Assemblies With Glycerol Monooleate

Valentin,

Kadakia,

Varidel

et al. 2024

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The antimicrobial peptide LL‐37 is a promising alternative to conventional antibiotics to combat bacteria in suspension and biofilms. Its self‐assembly with polar lipids is suggested to improve its potential for therapeutic applications with higher stability against degradation and bioavailability. This study investigates the self‐assembly of LL‐37 with glyceryl monooleate (GMO), establishing the link between colloidal structure and antimicrobial activity. Small‐angle X‐ray scattering, dynamic light scattering and cryogenic transmission electron microscopy show structural transformation from dispersions of inverse bicontinuous structure (cubosomes) to multilamellar vesicles and direct rod‐like mixed‐micelles upon increasing the content of LL‐37 in GMO. In vitro assays against planktonic and biofilm cells demonstrate that 128 µg mL−1 of GMO cubosomes have no impact on Pseudomonas aeruginosa. Still, the cubosomes reduce the Staphylococcus aureus planktonic population by ≈ 1‐log after 24 h. Cylindrical micelles formed at LL‐37/GMO 9/1 and 8/2 with 128 µg mL−1 LL‐37 decrease the Pseudomonas aeruginosa population by 6‐log. This activity is gradually abolished when LL‐37 is encapsulated in vesicles or cubosomes. They also demonstrate low antibiofilm efficacy and promote the biomass of Staphylococcus aureus biofilms. These results highlight the importance of colloidal structure for therapeutic outcomes, providing insights for advanced lipid nanocarrier designs.

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Implementation of Diverse Nano-cargos to Disguise and Fight Multidrug Resistance

Bollu

Parimi

Bhatt

et al. 2022

Emerging Modalities in Mitigation of Antimicrobial Resistance

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Bacterial lipase triggers the release of antibiotics from digestible liquid crystal nanoparticles

Cited by 43 publications

References 80 publications

Tobramycin Liquid Crystal Nanoparticles Eradicate Cystic Fibrosis‐Related Pseudomonas aeruginosa Biofilms

Tobramycin Liquid Crystal Nanoparticles Eradicate Cystic Fibrosis‐Related Pseudomonas aeruginosa Biofilms

Colloidal Structure Dictates Antimicrobial Efficacy in LL‐37 Self‐Assemblies With Glycerol Monooleate

Implementation of Diverse Nano-cargos to Disguise and Fight Multidrug Resistance

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