Rifampicin–Liposomes for Mycobacterium abscessus Infection Treatment: Intracellular Uptake and Antibacterial Activity Evaluation

Rinaldi, Federica; Hanieh, Patrizia Nadia; Sennato, Simona; Santis, Federica De; Forte, Jacopo; Fraziano, Maurizio; Casciardi, Stefano; Marianecci, Carlotta; Bordi, F.; Carafa, Maria

doi:10.3390/pharmaceutics13071070

Cited by 18 publications

(24 citation statements)

References 38 publications

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“…To increase the efficacy of these potent antimicrobials, a drug delivery system must be developed. One possible route is the creation of an MS-40S/MS-40-loaded liposome, as has been shown with rifampicin in the treatment of pulmonary Mycobacterium abscessus infections [ 54 ]. Creating an aerosolized antimicrobial therapy would also allow us to achieve higher concentrations of the drug, and increase lung penetration, which is especially important for CF pulmonary infections [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

New Auranofin Analogs with Antibacterial Properties against Burkholderia Clinical Isolates

Maydaniuk

Truong

et al. 2021

Antibiotics

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Bacteria of the genus Burkholderia include pathogenic Burkholderia mallei, Burkholderia pseudomallei and the Burkholderia cepacia complex (Bcc). These Gram-negative pathogens have intrinsic drug resistance, which makes treatment of infections difficult. Bcc affects individuals with cystic fibrosis (CF) and the species B. cenocepacia is associated with one of the worst clinical outcomes. Following the repurposing of auranofin as an antibacterial against Gram-positive bacteria, we previously synthetized auranofin analogs with activity against Gram-negatives. In this work, we show that two auranofin analogs, MS-40S and MS-40, have antibiotic activity against Burkholderia clinical isolates. The compounds are bactericidal against B. cenocepacia and kill stationary-phase cells and persisters without selecting for multistep resistance. Caenorhabditis elegans and Galleria mellonella tolerated high concentrations of MS-40S and MS-40, demonstrating that these compounds have low toxicity in these model organisms. In summary, we show that MS-40 and MS-40S have antimicrobial properties that warrant further investigations to determine their therapeutic potential against Burkholderia infections.

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Section: Discussionmentioning

confidence: 99%

New Auranofin Analogs with Antibacterial Properties against Burkholderia Clinical Isolates

Maydaniuk

Truong

et al. 2021

Antibiotics

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“…5 A thick layer of mycolic acid present on the MTB cell wall presents an additional, very effective barrier to the delivery of hydrophobic antitubercular agents such as rifampicin, assisting survival of the bacteria. 6 Of 41 known new antibiotics currently at various stages of development, none are designed to treat intracellular infections specifically. 7 In the absence of new antibiotic drugs, one alternative strategy is to improve the efficacy of currently available antibiotics via the use of microor nanocarriers, which improve delivery to the intracellular site of bacterial infection.…”

Section: ■ Introductionmentioning

confidence: 99%

“…A major issue with the current treatment of TB, in common with other intracellular infections such as salmonella, listeria, and urinary tract infections, relates to the intracellular location of the infection. , Difficulties in the transport of conventional antibiotics across the plasma membrane to the site of infection, in combination with natural macrophage defense mechanisms, can markedly reduce the efficacy of current treatments . A thick layer of mycolic acid present on the MTB cell wall presents an additional, very effective barrier to the delivery of hydrophobic antitubercular agents such as rifampicin, assisting survival of the bacteria . Of 41 known new antibiotics currently at various stages of development, none are designed to treat intracellular infections specifically .…”

Section: Introductionmentioning

confidence: 99%

“…RIF, which inhibits bacterial RNA synthesis, is one of the most powerful first-line anti-TB treatments and has been shown to reduce the duration of treatment. However, in common with other ATDs such as isoniazid, it is associated with adverse physiochemical properties such as poor water-solubility and high toxicity . Cubosomeslipid nanoparticle-based systems of internal cubic symmetrycan be designed to enhance the therapeutic index of drugs through improvement of delivery efficacy and reduction of drug toxicity.…”

Section: Introductionmentioning

confidence: 99%

“…However, in common with other ATDs such as isoniazid, it is associated with adverse physiochemical properties such as poor water-solubility and high toxicity. 6 Cubosomes�lipid nanoparticle-based systems of internal cubic symmetry�can be designed to enhance the therapeutic index of drugs through improvement of delivery efficacy and reduction of drug toxicity. These materials consist of a single lipid bilayer, which adopts the shape of an infinite periodic minimal surface and subdivides this space into two interpenetrating aqueous networks.…”

Section: ■ Introductionmentioning

confidence: 99%

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Cubosome Lipid Nanocarriers As a Drug Delivery Vehicle for Intracellular Mycobacterium tuberculosis Infections

Sarkar

Dyett

Lakic

et al. 2023

ACS Appl. Mater. Interfaces

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Mycobacterium tuberculosis (MTB) causes the infectious disease tuberculosis (TB), responsible for more deaths than any other single infectious disease in history. Intracellular MTB are slow growing and difficult to target with traditional antitubercular drugs, leading to the emergence of multidrug resistance in TB infection, which is a major global public health issue. Recent advances in innovative lipid nanotechnologies for drug delivery have demonstrated promising outcomes for chronic infectious diseases but have not yet been tested as potential delivery systems for intracellular infections such as TB. The current study evaluates the potential of monoolein (MO)-based cationic cubosomes for the encapsulation and delivery of the first line antitubercular drug rifampicin (RIF) against an MTB-H37Ra in vitro culture model. In particular, we show that the use of cationic cubosomes as delivery vehicles reduced the minimum inhibitory concentration (MIC) of RIF by 2-fold against actively replicating MTB-H37Ra (compared to that of the free drug) and also shortened the lifecycle duration of axenic MTB-H37Ra from 5 to 3 days. The cubosome-mediated delivery was also found to be effective against intracellular MTB-H37Ra within THP-1 human macrophages, with a 2.8 log reduction in viability of the bacilli after 6 days incubation at the MIC. The killing time was also reduced from 8 to 6 days without distressing the host macrophages. Mechanistic studies on the uptake of RIF-loaded cationic cubosomes using total internal reflection fluorescence microscopy (TIRFM) demonstrated the capacity of these lipid particles to effectively target intracellular bacteria. Overall, these results demonstrate that cationic cubosomes are a potent delivery system for the antitubercular drug RIF for therapeutic management of TB.

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Lipase‐Responsive Rifampicin‐Based Biodegradable PCL Nanocarrier for Antibacterial Treatment

et al. 2023

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Rifampicin (RFP) is a first‐line drug used to treat a variety of infections, including wound infections but has limitations in its use due to its toxicity. Hence, an urgent need exists for the development of suitable carriers for the delivery of the antibiotic. In this study, a novel approach is introduced for drug administration, employing stimulus‐responsive carriers to achieve an on‐demand strategy. This innovative method aims to minimize the dosage and frequency of drug administration, consequently lowering cytotoxicity levels. We used the lipases‐sensitive polycaprolactone (PCL) to produce nanocomposites loaded with rifampicin (PCL−RFP NPs). Nanoparticles were prepared by a single‐step emulsion solvent evaporation method. The size distribution of blank nanoparticles (PCL NPs) and PCL−RFP NPs were 172±30 nm and 229±58 nm, respectively. The liberation of RFP from PCL−RFP NPs was monitored over a period of 72 h in the absence and the presence of lipase was 9.46±0.24 % and 53.3±3.33 %, respectively, indicating responsive behavior. The minimum inhibitory concentration to lipase‐expressing Staphylococcus aureus (S. aureus) of PCL−RFP NPs was significantly improved compared to the free drug. Cytotoxicity tests using human dermal fibroblasts showed that the nanocomposites had better biocompatible when compared to the free drug. These findings indicate that the developed nanocomposite carriers have the potential to be promising candidates for delivering antibiotics in the field of biomedicine.

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Rifampicin–Liposomes for Mycobacterium abscessus Infection Treatment: Intracellular Uptake and Antibacterial Activity Evaluation

Cited by 18 publications

References 38 publications

New Auranofin Analogs with Antibacterial Properties against Burkholderia Clinical Isolates

New Auranofin Analogs with Antibacterial Properties against Burkholderia Clinical Isolates

Cubosome Lipid Nanocarriers As a Drug Delivery Vehicle for Intracellular Mycobacterium tuberculosis Infections

Lipase‐Responsive Rifampicin‐Based Biodegradable PCL Nanocarrier for Antibacterial Treatment

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