Preparation of Carrier-Free Inhalable Dry Powder of Rivaroxaban Using Two-Step Milling for Lung-Targeted Delivery DOI Creative Commons
Young‐Jin Kim,

Jaewoon Son,

Chang-Soo Han

и другие.

Pharmaceutics, Год журнала: 2025, Номер 17(5), С. 634 - 634

Опубликована: Май 9, 2025

Background/Objectives: This study aimed to develop a dry powder inhalation (DPI) formulation of rivaroxaban (RVX) using combination bead milling (BM) and jet (JM) enhance lung-targeted delivery for the effective treatment pulmonary embolism while minimizing systemic exposure. Methods: A carrier-free DPI RVX was developed sequential BM JM, with L-leucine incorporated at various concentrations (1%, 5%, 10%) as force control agent. The formulations were characterized particle morphology, size distribution, crystallinity, thermal properties. in-vitro aerodynamic performance evaluated next-generation impactor, ex-vivo studies assessed anticoagulant activity. Pharmacokinetic tissue distribution carried out in Sprague Dawley rats following intratracheal administration, effects inhaled compared those oral administration. Results: optimized BM-JM-5L achieved Dv50 2.58 ± 0.01 µm fine fraction 72.10 2.46%, indicating suitability delivery. two-step effectively reduced enhanced dispersibility without altering RVX’s physicochemical Ex-vivo anticoagulation tests confirmed maintained or improved In-vivo showed that administration (5 mg/kg) led 493-fold increase lung drug concentration 2.56-fold higher relative bioavailability vs. dosing, minimal heart accumulation, confirming targeted Conclusions: milled formulations, particularly 5% leucine, demonstrated significant potential by achieving high local concentrations, rapid onset, lower doses. These findings highlight feasibility treating embolism.

Язык: Английский

Special Issue: “New Trends in Diabetes, Hypertension, and Cardiovascular Diseases—2nd Edition” DOI Open Access
Yutang Wang, Dianna J. Magliano

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 449 - 449

Опубликована: Янв. 7, 2025

Cardiovascular diseases (CVDs) encompass a range of conditions affecting both the heart (e.g., coronary disease and failure [1]) blood vessels cerebrovascular [2] peripheral artery [3]) [...].

Язык: Английский

Процитировано

1

Integrated Care in Atrial Fibrillation: A Multidisciplinary Approach to Improve Clinical Outcomes and Quality of Life DOI Open Access
Ana Mónica Machado, Fernanda Leite, M. Graça Pereira

и другие.

Healthcare, Год журнала: 2025, Номер 13(3), С. 325 - 325

Опубликована: Фев. 5, 2025

Background: Atrial fibrillation (AF) is the most common arrhythmia globally, associated with serious complications such as stroke and heart failure, well significant impacts on patients’ quality of life. Objectives: This theoretical article explores role integrated care in management AF, highlighting need for a multidisciplinary approach that goes beyond rhythm rate control. Methods: Through review literature, this prevalence challenges diagnosis, socioeconomic psychological impact, benefits integrating medical, psychological, social interventions, drawing insights from studies about integrative AF. Results: The findings highlight managing including its high prevalence, complex patients. Integrated models, combining improve treatment adherence, reduce like enhance patient Conclusions: models hold promise improving outcomes AF patients through structured, approaches. Evidence supports reductions cardiovascular events, hospitalizations, mortality when adhering to clinical guidelines, emphasizing education, implementing individualized strategies. Despite challenges, regional disparities suboptimal implementation, integration teams emerging technologies offers way delivery accessibility. Future efforts should focus personalizing care, promoting professional collaboration, taking advantage technological advances optimize promote sustainable health systems.

Язык: Английский

Процитировано

1

Beyond Anticoagulation: A Comprehensive Review of Non-Vitamin K Oral Anticoagulants (NOACs) in Inflammation and Protease-Activated Receptor Signaling DOI Open Access
Shirin Jannati, Rajashree Patnaik, Yajnavalka Banerjee

и другие.

Опубликована: Июнь 20, 2024

Non-Vitamin K Oral Anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs—Apixaban, Rivaroxaban, Edoxaban, Dabigatran—not only as anticoagulants but also modulators inflammation via Protease-Activated Receptor (PAR) signaling. We highlight unique pharmacotherapeutic properties each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond established roles, emerging research suggests that NOACs influence through PAR signaling pathways, implicating factors such FXa Thrombin modulation inflammatory responses. synthesizes current evidence on anti-inflammatory potential NOACs, exploring impact markers conditions atherosclerosis diabetes. By delineating mechanisms which mediate effects, this work aims to expand therapeutic utility, new perspectives for managing diseases. Our findings underscore broader implications advocating consideration strategies aimed at addressing inflammation-related pathologies. comprehensive synthesis not enhances understanding NOACs' multifaceted paves way future applications cardiovascular health

Язык: Английский

Процитировано

5

Selective Modulation of PAR-2-Driven Inflammatory Pathways by Oleocanthal: Attenuation of TNF-α and Calcium Dysregulation in Colorectal Cancer Models DOI Open Access
Rajashree Patnaik, Riah Lee Varghese, Yajnavalka Banerjee

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 2934 - 2934

Опубликована: Март 24, 2025

Colorectal cancer (CRC) remains a principal contributor to oncological mortality worldwide, with chronic inflammation serving as fundamental driver of its pathogenesis. Protease-activated receptor-2 (PAR-2), G-protein-coupled receptor, orchestrates inflammation-driven tumorigenesis by potentiating NF-κB and Wnt/β-catenin signaling, thereby fostering epithelial-mesenchymal transition (EMT), immune evasion, therapeutic resistance. Despite pathological significance, targeted modulation PAR-2 an underexplored avenue in CRC therapeutics. Oleocanthal (OC), phenolic constituent extra virgin olive oil, is recognized for potent anti-inflammatory anti-cancer properties; however, regulatory influence on signaling yet be elucidated. This study interrogates the impact OC PAR-2-mediated inflammatory cascades using HT-29 Caco-2 cell lines subjected lipopolysaccharide (LPS)-induced activation PAR-2. Expression levels TNF-α were quantified through Western blotting RT-PCR, while ELISA assessed secretion. Intracellular calcium flux, pivotal modulator PAR-2-driven oncogenic inflammation, was evaluated via Fluo-4 assays. LPS markedly elevated expression at both mRNA protein cells (p < 0.01, one-way ANOVA). administration (20-150 μg/mL) elicited dose-dependent suppression PAR-2, maximal inhibition 100-150 μg/mL 0.001, Tukey's post hoc test). Concomitant reductions transcription 0.01) secretion 0.001) observed, corroborating efficacy OC. Additionally, ameliorated LPS-induced dysregulation, restoring intracellular homeostasis concentration-dependent manner 0.01). Crucially, exhibited selectivity leaving PAR-1 unaltered > 0.05), underscoring precision agent. These findings position selective CRC, disrupting pro-tumorigenic microenvironment attenuation secretion, pathways. furnishes mechanistic insights into OC's potential nutraceutical intervention inflammation-associated CRC. Given variability bioavailability content commercial future investigations should delineate optimal dosing strategies vivo advance translational therapy.

Язык: Английский

Процитировано

0

Preparation of Carrier-Free Inhalable Dry Powder of Rivaroxaban Using Two-Step Milling for Lung-Targeted Delivery DOI Creative Commons
Young‐Jin Kim,

Jaewoon Son,

Chang-Soo Han

и другие.

Pharmaceutics, Год журнала: 2025, Номер 17(5), С. 634 - 634

Опубликована: Май 9, 2025

Background/Objectives: This study aimed to develop a dry powder inhalation (DPI) formulation of rivaroxaban (RVX) using combination bead milling (BM) and jet (JM) enhance lung-targeted delivery for the effective treatment pulmonary embolism while minimizing systemic exposure. Methods: A carrier-free DPI RVX was developed sequential BM JM, with L-leucine incorporated at various concentrations (1%, 5%, 10%) as force control agent. The formulations were characterized particle morphology, size distribution, crystallinity, thermal properties. in-vitro aerodynamic performance evaluated next-generation impactor, ex-vivo studies assessed anticoagulant activity. Pharmacokinetic tissue distribution carried out in Sprague Dawley rats following intratracheal administration, effects inhaled compared those oral administration. Results: optimized BM-JM-5L achieved Dv50 2.58 ± 0.01 µm fine fraction 72.10 2.46%, indicating suitability delivery. two-step effectively reduced enhanced dispersibility without altering RVX’s physicochemical Ex-vivo anticoagulation tests confirmed maintained or improved In-vivo showed that administration (5 mg/kg) led 493-fold increase lung drug concentration 2.56-fold higher relative bioavailability vs. dosing, minimal heart accumulation, confirming targeted Conclusions: milled formulations, particularly 5% leucine, demonstrated significant potential by achieving high local concentrations, rapid onset, lower doses. These findings highlight feasibility treating embolism.

Язык: Английский

Процитировано

0