Persistent microbial infections and idiopathic pulmonary fibrosis - an insight into non-typeable Haemophilus influenza pathogenesis DOI Creative Commons

Anthony Shadid,

Helen E. Rich,

Hunter DeVaughn

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Dec. 20, 2024

Interstitial lung disease (ILD) is characterized by chronic inflammation and scarring of the lungs, which idiopathic pulmonary fibrosis (IPF) most devastating pathologic form. Idiopathic pathogenesis leads to loss function eventual death in 50% patients, making it leading cause ILD-associated mortality worldwide. Persistent subclinical microbial infections are implicated acute exacerbation diseases. However, while epidemiological studies have highlighted pollutants, gastric aspirate, as major causes for progression IPF, role persistent IPF remains unclear. In this review, we focused on infections, including viral, bacterial, fungal their mechanisms action IPF. particular, Gram-negative bacteria Non-typeable Haemophilus influenzae ( NTHi ) ILDs discussed, along with growing evidence its given unique ability establish intracellular leveraging non-capsulated nature evade host defenses. While antibiotic treatments presumably beneficial target extracellular, interstitial, systemic burden pathogens, effects significantly reduced combating pathogens that reside compartments. The review also includes recent clinical trials, center combinatorial involving antimicrobials immunosuppressants, antifibrotic drugs help mitigate patients. Finally, future directions focus mRNA-based therapeutics, demonstrated effectiveness across a wide range applications feasibility targeting pathogens.

Language: Английский

Zwitterionic Polymer-Functionalized Lipid Nanoparticles for the Nebulized Delivery of mRNA DOI
Allen Yujie Jiang, Sushil Lathwal,

Sabrina Meng

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(47), P. 32567 - 32574

Published: Nov. 13, 2024

Lipid nanoparticles (LNPs) have great potential to enable inhaled delivery of mRNA treat pulmonary diseases. However, this has been limited by the challenge nebulizing LNPs. Nebulization LNPs can cause aggregate and release encapsulated mRNA, limiting their efficacy. To overcome challenge, are developed whereby PEG-lipid is fully replaced with a zwitterionic polymer (ZIP)-lipid conjugate greatly enhance nebulizer stability. formulated ZIP-lipids (ZIP-LNPs) were stable nebulization across wide range formulation parameters. The optimized ZIP-LNP formulation, containing reduced cholesterol content relative traditional LNPs, demonstrated improved in both healthy mucoobstructed mouse lungs. Repeat administration was well tolerated did not result inflammation. This study demonstrates polymer-lipid conjugates for improving performance mRNA-LNP formulations.

Language: Английский

Citations

4
Hydrogen-induced disruption of the airway mucus barrier enhances nebulized RNA delivery to reverse pulmonary fibrosis DOI Creative Commons
Chang Liu,

Xidong Tian,

Zhenping Wang

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(16)

Published: April 16, 2025

Nebulized RNA therapies are well suited for treating respiratory diseases, in particular pulmonary fibrosis (PF); however, effective delivery remains challenging. In this study, we present a highly efficient aerosol inhalation system that enables high levels of vivo transfection efficiency lung macrophages, yielding durable responses against PF. First, established nose-only device integrated with hydrogen supplement system. This setup the precise administration lipid nanoparticles (LNPs) at controlled low dose, while simultaneously delivering optimal concentration therapeutic gas. We further developed hybrid NP (HNP) by hybridizing pH-dependent charge-inverting film apoptotic T cell membranes to enhance endosomal escape and trigger macrophage production hepatocyte growth factor repair. demonstrated flow–induced shear stresses disrupt NP-mucus interaction, enhancing deposition aerosolized HNPs/ TGF β 1 siRNA within fibrotic lesions, effectively blocking fibrogenic signaling pathways offering clinically viable strategy combating

Language: Английский

Citations

0
Nanomaterials for the Treatment of Lung Cancer: The Role of Natural Products DOI
Luis Francisco Salomé-Abarca, Daniel Hernández‐Patlan, Bruno Solís-Cruz

et al.

Interdisciplinary cancer research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Effects of Surface Charge of Inhaled Liposomes on Drug Efficacy and Biocompatibility DOI Creative Commons

Jinniu Zhang,

Yun Huang,

Wenhao Shen

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(3), P. 329 - 329

Published: March 3, 2025

Objectives: Liposomes are a promising drug carrier for inhaled delivery systems and their physical parameters could influence therapeutic efficacy significantly. This study was designed to answer the specific question of proper surface charge liposomes in pulmonary inhalation, as well synergistic anti-inflammation between drugs. Methods: In this work, series drug-loaded with different charges (from negative positive) were prepared, several vitro vivo assays, including cytotoxicity, hemolysis assay, mucus penetration lipopolysaccharide (LPS)-induced pneumonia model test, adopted evaluate biocompatibility above liposomes. Results: Compared cationic liposomes, anionic capable better good (low blood compatibility mild tissue inflammation), but poor cellular uptake by immune cells. specific, even when liposome only +2.6 mV, its cytotoxicity reached around 20% 15%, respectively. Furthermore, there no significant difference (−25.9 vs. −2.5 mV), slightly negative-charged exhibited uptake. Conclusions: Thus, (−1~−3 mV) be considering both biocompatibility. an LPS-induced mouse model, achieved anti-inflammatory compared free

Language: Английский

Citations

0
An Advanced Inhalable Dry Powder, Mucus-Penetrating Aerosol Platform: Bridging Andrographolide Delivery with Clinical Translation DOI
Decui Cheng, Tingting Pan, Xiaoli Wang

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: unknown, P. 123401 - 123401

Published: May 1, 2025

Language: Английский

Citations

0
Persistent microbial infections and idiopathic pulmonary fibrosis - an insight into non-typeable Haemophilus influenza pathogenesis DOI Creative Commons

Anthony Shadid,

Helen E. Rich,

Hunter DeVaughn

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Dec. 20, 2024

Interstitial lung disease (ILD) is characterized by chronic inflammation and scarring of the lungs, which idiopathic pulmonary fibrosis (IPF) most devastating pathologic form. Idiopathic pathogenesis leads to loss function eventual death in 50% patients, making it leading cause ILD-associated mortality worldwide. Persistent subclinical microbial infections are implicated acute exacerbation diseases. However, while epidemiological studies have highlighted pollutants, gastric aspirate, as major causes for progression IPF, role persistent IPF remains unclear. In this review, we focused on infections, including viral, bacterial, fungal their mechanisms action IPF. particular, Gram-negative bacteria Non-typeable Haemophilus influenzae ( NTHi ) ILDs discussed, along with growing evidence its given unique ability establish intracellular leveraging non-capsulated nature evade host defenses. While antibiotic treatments presumably beneficial target extracellular, interstitial, systemic burden pathogens, effects significantly reduced combating pathogens that reside compartments. The review also includes recent clinical trials, center combinatorial involving antimicrobials immunosuppressants, antifibrotic drugs help mitigate patients. Finally, future directions focus mRNA-based therapeutics, demonstrated effectiveness across a wide range applications feasibility targeting pathogens.

Language: Английский

Citations

0