AI Article Synopsis
- Idiopathic pulmonary fibrosis is a chronic lung disease caused by progressive damage to lung tissue.
- A study developed a nintedanib and hydroxypropyl-γ-cyclodextrin (HP-γ-CyD) inclusion complex to enhance the drug's effectiveness when delivered directly to the lungs.
- This complex improved the stability and distribution of nintedanib in the lungs, reduced fibrosis, and could expand treatment options for patients with idiopathic pulmonary fibrosis.
Article Abstract
Idiopathic pulmonary fibrosis is a chronic lung disease that is characterized by progressive abnormal reprogramming following injury of the pulmonary structure. In this study, we prepared a nintedanib (antifibrotic agent) and cyclodextrin (CyD) inclusion complex to improve the pharmacokinetics and antifibrotic effects of nintedanib following intrapulmonary administration. Hydroxypropyl-γ-CyD (HP-γ-CyD) enhanced the solubility of nintedanib without cytotoxic effects on WI-38 cells (lung fibroblasts) and NCI-H441 cells (alveolar epithelium model). Compared with nintedanib ethanesulfonate salt, the nintedanib-HP-γ-CyD inclusion complex exhibited prolonged distribution in the lungs following intrapulmonary administration in mice with bleomycin-induced pulmonary fibrosis. In addition, compared with nintedanib ethanesulfonate salt, the nintedanib-HP-γ-CyD inclusion complex exhibited higher stability in the bronchoalveolar lavage fluid and lower permeability in NCI-H441 cell monolayers. These results suggested that the inclusion complexation of nintedanib into HP-γ-CyD improved its pharmacokinetics following intrapulmonary administration by increasing its stability in the lungs and reducing its permeability through the alveolar cell membrane. Intrapulmonary administration of the nintedanib-HP-γ-CyD inclusion complex significantly reduced the intrapulmonary hydroxyproline content and limited pathological fibrotic changes. Overall, this study indicates that antifibrotic agent-CyD inclusion complexation intended for intrapulmonary administration can be used to prolong distribution in the lungs and lead to the expansion of idiopathic pulmonary fibrosis therapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejpb.2022.02.009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TARGETING LUNG HEME IRON BY AEROSOL HEMOPEXIN ADMINSTRATION IN SICKLE CELL DISEASE PULMONARY HYPERTENSION.
Free Radic Biol Med
January 2025
University of Colorado, Anschutz Medical Campus School of Medicine| Translational research laboratory of Red Blood Cell Diseases and Hypoxia related illnesses| Cardiovascular Pulmonary Research (CVP) group, Pediatrics. Electronic address:
Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH.
View Article and Find Full Text PDFEvaluation of the Effect of the Live Vaccine (Strain 168) in Ningxiang Pigs.
Vaccines (Basel)
November 2024
National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
[Background/Objectives] () is widespread in the global swine industry, leading to significant economic losses, and is particularly severe in native Chinese pig breeds. The Ningxiang pig, a well-known native breed in China, is susceptible to , exhibiting high morbidity and mortality rates. This study was designed to evaluate the clinical effectiveness of the live vaccine (strain 168).
View Article and Find Full Text PDFVentilation and features of the lung environment dynamically alter modeled intrapulmonary aerosol exposure from inhaled electronic cigarettes.
Sci Rep
December 2024
Division of Pulmonary and Critical Care, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1690, USA.
Electronic cigarettes (e-cigs) fundamentally differ from tobacco cigarettes in their generation of liquid-based aerosols. Investigating how e-cig aerosols behave when inhaled into the dynamic environment of the lung is important for understanding vaping-related exposure and toxicity. A ventilated artificial lung model was developed to replicate the ventilatory and environmental features of the human lung and study their impact on the characteristics of inhaled e-cig aerosols from simulated vaping scenarios.
View Article and Find Full Text PDFLPS Increases Artery but Not Airway Contraction in Precision Cut Lung Slices from a Mouse Model of ARDS.
Am J Respir Cell Mol Biol
December 2024
Monash University, Department of Pharmacology, Biomedicine Discovery Institute, Clayton, Victoria, Australia.
Acute respiratory distress syndrome (ARDS) results in decreased quality of life, including increased risk of pulmonary hypertension (PH). In animal models, ARDS can be induced by lipopolysaccharide (LPS), which can disrupt the pulmonary endothelium and epithelium and induce inflammation. We tested whether administration or treatment with LPS alters the reactivity of intrapulmonary arteries and airways to constrictors relevant to both ARDS and PH, using the precision cut lung slice (PCLS) technique.
View Article and Find Full Text PDFPharmacokinetics of Omadacycline in Adults with Cystic Fibrosis.
Clin Pharmacokinet
December 2024
Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA.
Background: Omadacycline offers a potential advancement in the management of infections in people with cystic fibrosis (CF) because of its spectrum of activity, intrapulmonary penetration, and oral bioavailability. A prospective single-dose, single-arm study was conducted to characterize the pharmacokinetic (PK) profile of omadacycline in people with CF, considering the known alterations in PK observed in this population (NCT04460586, 2020-07-01).
Methods: Plasma samples were obtained from nine adults with CF who received a single dose of intravenous omadacycline 100 mg over 0.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!