Pulmonary Administration: Strengthening the Value of Therapeutic Proximity

Videira, Mafalda; Llop, Jordi; Sousa, Carolina; Kreutzer, B; Cossío, Unai; Forbes, Ben; Vieira, Isabel; Gil, Nuno; Silva‐Lima, Beatriz

doi:10.3389/fmed.2020.00050

Cited by 14 publications

(6 citation statements)

References 81 publications

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“…The lung is an attractive route for noninvasive drug delivery, with many advantages, such as a high surface area with rapid absorption due to high vascularity and circumvention of the first pass effect. Aerosol drug delivery is commonly used to treat respiratory conditions (11) and is being actively investigated for systemic applications in multiple diseases (12). Nanoparticles expand the therapeutic potential of certain drugs as they can facilitate drug delivery via different routes, including inhalation (13).…”

Section: Introductionmentioning

confidence: 99%

Nano-chemically Modified Tetracycline-3 (nCMT-3) Attenuates Acute Lung Injury via Blocking sTREM-1 Release and NLRP3 Inflammasome Activation

Meng

Wang

Guo

et al. 2022

Shock

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Background: Intratracheal (IT) lipopolysaccharide (LPS) causes severe acute lung injury (ALI) and systemic inflammation. CMT-3 has pleiotropic anti-inflammatory effects including matrix metalloproteinase (MMP) inhibition, attenuation of neutrophil (PMN) activation, and elastase release. CMT-3's poor water solubility limits its bioavailability when administered orally for treating ALI. We developed a nano-formulation of to test the hypothesis that the pleiotropic anti-inflammatory activities of IT nCMT-3 can attenuate LPS-induced ALI. Methods: C57BL/6 mice were treated with aerosolized IT nCMT-3 or saline, then had IT LPS or saline administered 2 h later. Tissues were harvested at 24 h. The effects of LPS and nCMT-3 on ALI were assessed by lung histology, MMP level/activity (zymography), NLRP3 protein, and activated caspase-1 levels. Blood and bronchoalveolar lavage fluid (BALF) cell counts, PMN elastase, and soluble triggering receptor expressed on myelocytes-1 (sTREM-1) levels, TNF-a, IL-1b, IL-6, IL-18, and BALF protein levels were also measured. Results: LPS-induced ALI was characterized by histologic lung injury (PMN infiltration, alveolar thickening, edema, and consolidation) elevated proMMP-2, -9 levels and activity, increased NLRP-3 protein and activated caspase-1 levels in lung tissue. LPS-induced increases in plasma and BALF levels of sTREM-1, TNF-a, IL-1b, IL-6, IL-18, PMN elastase and BALF protein levels demonstrate significant lung/systemic inflammation and capillary leak. nCMT-3 significantly ameliorated all of these LPS-induced inflammatory markers to control levels, and decreased the incidence of ALI. Conclusions: Pre-treatment with nCMT3 significantly attenuates LPS-induced lung injury/inflammation by multiple mechanisms including: MMP activation, PMN elastase, sTREM-1 release, and NLRP3 inflammasome/caspase-1 activation.

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Section: Introductionmentioning

confidence: 99%

Nano-chemically Modified Tetracycline-3 (nCMT-3) Attenuates Acute Lung Injury via Blocking sTREM-1 Release and NLRP3 Inflammasome Activation

Meng

Wang

Guo

et al. 2022

Shock

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“…The main factor limiting the use of siRNAs to suppress therapeutic targets in the lungs is the lack of an effective delivery scheme. Intranasal, intratracheal, or orotracheal administration of siRNA pre-complexed with liposomes, particles, or dendrimers is used in experimental schemes for administering siRNA-based drugs to mice [ 126 ]. These schemes take into account the characteristics of the respiratory tract of the mouse, allowing for effective intranasal administration to the lungs.…”

Section: Discussionmentioning

confidence: 99%

siRNA-Mediated Timp1 Silencing Inhibited the Inflammatory Phenotype during Acute Lung Injury

Chernikov

Staroseletz

Татарникова

et al. 2023

IJMS

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Acute lung injury is a complex cascade process that develops in response to various damaging factors, which can lead to acute respiratory distress syndrome. Within this study, based on bioinformatics reanalysis of available full-transcriptome data of acute lung injury induced in mice and humans by various factors, we selected a set of genes that could serve as good targets for suppressing inflammation in the lung tissue, evaluated their expression in the cells of different origins during LPS-induced inflammation, and chose the tissue inhibitor of metalloproteinase Timp1 as a promising target for suppressing inflammation. We designed an effective chemically modified anti-TIMP1 siRNA and showed that Timp1 silencing correlates with a decrease in the pro-inflammatory cytokine IL6 secretion in cultured macrophage cells and reduces the severity of LPS-induced acute lung injury in a mouse model.

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“…This makes the pulmonary route of drug delivery an excellent option in the treatment of SARS-CoV-2 infections. In the pulmonary route, the drugs are directly carried to the airway and alveolar epithelia in higher concentrations, and the drug come into direct contact with the pathological lung epithelia, thus providing a rapid onset of action which leads in the reduction of respiratory distress symptoms and lung occlusions . Nanoformulations of systemic antivirals, anti-inflammatory drugs, and glucocorticoids can be administered via the pulmonary route for the efficient treatment of SARS-CoV-2 infections.…”

Section: Therapeutic Nanoconstructs In Covid-19 Therapymentioning

confidence: 99%

Architectured Therapeutic and Diagnostic Nanoplatforms for Combating SARS-CoV-2: Role of Inorganic, Organic, and Radioactive Materials

Pandey

Nikam

Mutalik

et al. 2020

ACS Biomater. Sci. Eng.

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Although extensive research is being done to combat SARS-CoV-2, we are yet far away from a robust conclusion or strategy. With an increased amount of vaccine research, nanotechnology has found its way into vaccine technology. Researchers have explored the use of various nanostructures for delivering the vaccines for enhanced efficacy. Apart from acting as delivery platforms, multiple studies have shown the application of inorganic nanoparticles in suppressing the growth as well as transmission of the virus. The present review gives a detailed description of various inorganic nanomaterials which are being explored for combating SARS-CoV-2 along with their role in suppressing the transmission of the virus either through air or by contact with inanimate surfaces. The review further discusses the use of nanoparticles for development of an antiviral coating that may decrease adhesion of SARS-CoV-2. A separate section has been included describing the role of nanostructures in biosensing and diagnosis of SARS-CoV-2. The role of nanotechnology in providing an alternative therapeutic platform along with the role of radionuclides in SARS-CoV-2 has been described briefly. Based on ongoing research and commercialization of this nanoplatform for a viral disease, the nanomaterials show the potential in therapy, biosensing, and diagnosis of SARS-CoV-2.

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Pulmonary Administration: Strengthening the Value of Therapeutic Proximity

Cited by 14 publications

References 81 publications

Nano-chemically Modified Tetracycline-3 (nCMT-3) Attenuates Acute Lung Injury via Blocking sTREM-1 Release and NLRP3 Inflammasome Activation

Nano-chemically Modified Tetracycline-3 (nCMT-3) Attenuates Acute Lung Injury via Blocking sTREM-1 Release and NLRP3 Inflammasome Activation

siRNA-Mediated Timp1 Silencing Inhibited the Inflammatory Phenotype during Acute Lung Injury

Architectured Therapeutic and Diagnostic Nanoplatforms for Combating SARS-CoV-2: Role of Inorganic, Organic, and Radioactive Materials

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