Antitubercular nanocarrier monotherapy: Study of In Vivo efficacy and pharmacokinetics for rifampicin

Trousil, Jiří; Pavliš, Oto; Kubíčková, Pavla; Škorič, M.; Marešová, Vilma; Pavlová, Ewa; Knudsen, Kenneth Dahl; Dai, You-Shan; Zimmerman, Matthew; Dartois, Véronique; Fang, Jia‐You; Hrubý, Martin

doi:10.1016/j.jconrel.2020.02.026

Cited by 29 publications

(23 citation statements)

References 41 publications

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“…[ 45 ] The pharmacokinetics, pharmacodynamics, and anti‐TB efficacy of the nanoformulated RIF were further assessed in a mouse model (BALB/c mice infected intranasally with Mtb H37Rv) as a clinically relevant in vivo model. [ 64 ] Biodistribution study revealed that the nanoparticles were found mainly in the liver and in intestinal tissue, i.e., macrophage‐rich organs. The nanoparticles were well tolerated, compared to free RIF, RIF‐loaded nanoparticles showed improved pharmacokinetic and pharmacodynamic parameters with higher serum and lung RIF level.…”

Section: Nanotechnology‐based Drug Delivery Systemsmentioning

confidence: 99%

“…Importantly, the treatment with drug‐loaded nanoparticles was preferred as significantly less granulomas were observed compared to the treatment with the free drug. [ 64 ]…”

Section: Nanotechnology‐based Drug Delivery Systemsmentioning

confidence: 99%

“…[45] The pharmacokinetics, pharmacodynamics, and anti-TB efficacy of the nanoformulated RIF were further assessed in a mouse model (BALB/c mice infected intranasally with Mtb H37Rv) as a clinically relevant in vivo model. [64] Biodistribution study revealed that the nanoparticles were found mainly in the liver and in intestinal tissue, i.e., macrophage-rich organs. The nanoparticles Rapid, high-level accumulation in monocytes and neutrophils, and less efficient uptake by B and T cells in human PBMC; colocalization with Mtb H37Rv in phagosomes of dTHP-1; in M. marinum-infected zebra fish model NPs were taken up by macrophages; NPs had better activity in reducing bacterial burden and granuloma number [65] PLGA NPs, other type of NPs RIF, several fluorescent dyes Rapid NP uptake by macrophages and lowered bacterial load in M. marinum-infected zebra fish model; NP accumulation in granulomas in zebra fish model and in C57BL/6 mice (intranasally infected with Mtb) following intravenous administration [66,67] Niosomes (Span 60, Span 85, cholesterol, dicetyl phosphate, stearylamine) ETB Sustained release of drug in Swiss albino mice lungs after subcutaneous injection of niosomes; enhanced efficiency in decreasing bacterial counts in lung of guinea pigs (infected by intramuscular injection of Mtb H37Rv) after subcutaneous injection [68] PLGA NPs Ethionamide (ETH) Enhanced bioavailability of NPs when administered orally compared to free drug; ETH detected in lung, liver, and spleen, and no toxic effects were found in Swiss albino mice [69,70] Chitosan-dextran sulfate nanoparticles…”

Section: Passive Targetingmentioning

confidence: 99%

“…Importantly, the treatment with drug-loaded nanoparticles was preferred as significantly less granulomas were observed compared to the treatment with the free drug. [64] Zebrafish larvae have emerged as a vertebrate animal model since they gather unique characteristics like transparency, ease of manipulation, an innate immune response, and high degree of similarities with human genome. Importantly, granulomas formed in M. marinum-infected zebra fish model resemble human Mtb granulomas to a greater extent than that of the Mtb in a mouse model.…”

Section: Passive Targetingmentioning

confidence: 99%

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Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

Baranyai

Soria‐Carrera

Alleva

et al. 2020

Advanced Therapeutics

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The appearance and rapid spread of drug resistant strains of tuberculosis (TB), one of the deadliest infectious diseases, pose a serious threat to public health and increase the need for shorter, less toxic, and more effective therapies. Developing new drugs is difficult and often associated with side effects, so nanotechnology has emerged as a tool to improve current treatments and to rescue drugs having elevated toxicity or poor solubility. Due to their size and surface chemistry, antimicrobial‐loaded nanocarriers are avidly taken up by macrophages, the main cells hosting Mycobacterium tuberculosis. Macrophages are continuously recruited to infected areas, they can transport drugs with them, making passive targeting a good strategy for TB treatment. Active targeting (decorating surface of nanocarriers with ligands specific to receptors displayed by macrophages) further increases local drug concentration, and thus treatment efficacy. Although in in vivo studies, nanocarriers are often administered intravenously in order to avoid inaccurate dosage in animals, translation to humans requires more convenient routes like pulmonary or oral administration. This report highlights the importance and progress of pulmonary administration, passive and active targeting strategies toward bacteria reservoirs to overcome the challenges in TB treatment.

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Section: Nanotechnology‐based Drug Delivery Systemsmentioning

confidence: 99%

“…Importantly, the treatment with drug‐loaded nanoparticles was preferred as significantly less granulomas were observed compared to the treatment with the free drug. [ 64 ]…”

Section: Nanotechnology‐based Drug Delivery Systemsmentioning

confidence: 99%

Section: Passive Targetingmentioning

confidence: 99%

Section: Passive Targetingmentioning

confidence: 99%

See 2 more Smart Citations

Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

Baranyai

Soria‐Carrera

Alleva

et al. 2020

Advanced Therapeutics

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show abstract

“…15,19,21 Moreover, rapid depletion of drug plasma levels due to excretion or first-pass metabolism can be avoided, and sustained drug release from NPs could enable a reduced frequency of administration. 16,17 Therefore, in TB therapy, NPs have great potential to increase treatment efficacy and patient compliance, 20,[22][23][24][25] which could impede the development of drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Π-Π Interactions Stabilize PeptoMicelle-Based Formulations of Pretomanid Derivatives Leading to Promising Therapy Against Tuberculosis in Zebrafish and Mouse Models

Dal

Schäfer

Thompson

et al. 2022

Preprint

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Tuberculosis is the deadliest bacterial disease globally, threatening the lives of millions every year. New antibiotic therapies that can shorten the duration of treatment, improve cure rates, and impede the development of drug resistance are desperately needed. Here, we used polymeric micelles to encapsulate four second-generation derivatives of the antitubercular drug pretomanid that had previously displayed much better in vivo activity against Mycobacterium tuberculosis than pretomanid itself. Because these compounds were relatively hydrophobic, we expected that such micellar formulations would increase drug bioavailability, reduce toxicities, and improve therapeutic outcomes. The polymeric micelles were based on polypept(o)ides (PeptoMicelles) and were stabilized in their hydrophobic core by Π-Π interactions, allowing the efficient encapsulation of aromatic pretomanid derivatives. The stability of these Π-Π stabilized PeptoMicelles was demonstrated in water, blood plasma, and lung surfactant by fluorescence cross-correlation spectroscopy and was further supported by prolonged circulation times of several days in the vasculature of zebrafish larvae. The pretomanid derivative with the best in vitro potency against Mycobacterium marinum ('drug D') was also the most efficacious PeptoMicelle formulation tested in the zebrafish larvae infection model, almost completely eradicating the bacteria at non-toxic doses. This lead formulation was further assessed against Mycobacterium tuberculosis in the susceptible C3HeB/FeJ mouse model, which develops human-like necrotic granulomas. Following intravenous administration, the drug D micellar formulation significantly reduced bacterial burden and inflammatory responses in the lungs and spleens of infected mice.

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Targeted Drug Delivery for Antimalarial Therapy

Zwayen

Zwain

Singh

2022

Drug Development for Malaria

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Antitubercular nanocarrier monotherapy: Study of In Vivo efficacy and pharmacokinetics for rifampicin

Cited by 29 publications

References 41 publications

Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

Π-Π Interactions Stabilize PeptoMicelle-Based Formulations of Pretomanid Derivatives Leading to Promising Therapy Against Tuberculosis in Zebrafish and Mouse Models

Targeted Drug Delivery for Antimalarial Therapy

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