Advanced Spray-Dried Inhalable Microparticles/Nanoparticles of an Innovative Mitophagy Activator for Targeted Lung Delivery: Design, Comprehensive Characterization, Human Lung Cell Culture, and In Vitro Aerosol Dispersion Performance DOI Creative Commons
Hasham S. Sofi,

Andrea J. Lora,

Haley M. Donow

и другие.

ACS Pharmacology & Translational Science, Год журнала: 2024, Номер 7(11), С. 3540 - 3558

Опубликована: Окт. 15, 2024

Urolithin A (UA) has demonstrated the ability to stimulate mitophagy and enhance mitochondrial cellular health in skeletal muscles humans after oral administration. It is hypothesized that targeted delivery of UA as inhaled dry powders lungs will through biogenesis. This study aimed engineer inhalable excipient-free powder inhalers (DPIs) for pulmonary delivery. The particles were designed by particle engineering from dilute organic solutions using state-of-the-art spray drying technology a closed mode. Comprehensive physicochemical characterization advanced microscopy techniques conducted examine phase behavior, molecular properties, which are necessary rational design inhalation aerosols. Molecular fingerprinting was attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy Raman spectroscopy. Chemical imaging mapping confocal (CRM) IR microscopy. spray-dried (SD) successfully produced at different spraying pump feed rates exhibited favorable properties. SD outstanding vitro aerosol dispersion performance with an FDI-approved human DPI device (Neohaler) correlated rate. In

Язык: Английский

Appeal of Urolithins from Synthesis to Biological Activities DOI
Hua Xu,

Danyu Lv,

Yongguang Guan

и другие.

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 29, 2025

Urolithins (Uros), a series of natural polyphenols derived from ellagic acid through gut bacteria metabolism, have gathered significant attention due to their diverse bioactivities such as maintaining mitochondrial health and anti-inflammatory antioxidative effects. However, the ability metabolize Uros varies among individuals. This Review provides comprehensive insight into synthesis, encapsulation Uros, focusing on biotransformation in vivo. We highlight critical role microbiota urolithins, including primary bacterial species Gordonibacter urolithinfaciens, Enterocloster bolteae Enterococcus faecium. Furthermore, therapeutic potential alleviating neurodegenerative diseases, cancer, Duchenne muscular dystrophy is discussed. Finally, several strategies for enhancing solubility bioavailability are summarized. Future research direction includes identifying key genes involved biotransformation, elucidating bioactive mechanisms improving bioavailability. In conclusion, we synthesized biosynthetic pathways properties better utilization management.

Язык: Английский

Процитировано

0

Design and Synthesis of O‐Dialkylaminoalkyl Substituted Urolithin Derivatives: DNA Topoisomerase IIα Inhibition With Promising Antiproliferative Activity DOI

Xintong Li,

Xiaochun Zhang,

Chan Yin

и другие.

Archiv der Pharmazie, Год журнала: 2025, Номер 358(5)

Опубликована: Май 1, 2025

ABSTRACT Based on the pharmacophore structural characteristics of topoisomerase II (TopoII) inhibitors: (i) planar polyaromatic skeleton; (ii) cation core; (iii) a groove‐binding side chain moiety, 16 urolithin derivatives with O ‐dialkylaminoalkyl substitutions were designed and synthesized. Most synthesized compounds showed improved TopoIIα inhibitory antiproliferative activities. 20 best activity also exhibited excellent IC 50 values 0.91 ± 0.01, 1.93 0.04, 2.84 0.34 μM against MDA‐MB‐231, HeLa, A549 cell lines, being about 12.55, 3.95, 2.17 times more active than VP‐16 (IC 11.42 0.82, 7.63 0.46, 6.15 0.43 μM, respectively). Meanwhile, weak toxicity to normal cells. In addition, exerted anti‐migration anti‐invasion MDA‐MB‐231 Our results supported that might act as inhibitor potential become new type antitumor drug lead.

Язык: Английский

Процитировано

0

Advanced Spray-Dried Inhalable Microparticles/Nanoparticles of an Innovative Mitophagy Activator for Targeted Lung Delivery: Design, Comprehensive Characterization, Human Lung Cell Culture, and In Vitro Aerosol Dispersion Performance DOI Creative Commons
Hasham S. Sofi,

Andrea J. Lora,

Haley M. Donow

и другие.

ACS Pharmacology & Translational Science, Год журнала: 2024, Номер 7(11), С. 3540 - 3558

Опубликована: Окт. 15, 2024

Urolithin A (UA) has demonstrated the ability to stimulate mitophagy and enhance mitochondrial cellular health in skeletal muscles humans after oral administration. It is hypothesized that targeted delivery of UA as inhaled dry powders lungs will through biogenesis. This study aimed engineer inhalable excipient-free powder inhalers (DPIs) for pulmonary delivery. The particles were designed by particle engineering from dilute organic solutions using state-of-the-art spray drying technology a closed mode. Comprehensive physicochemical characterization advanced microscopy techniques conducted examine phase behavior, molecular properties, which are necessary rational design inhalation aerosols. Molecular fingerprinting was attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy Raman spectroscopy. Chemical imaging mapping confocal (CRM) IR microscopy. spray-dried (SD) successfully produced at different spraying pump feed rates exhibited favorable properties. SD outstanding vitro aerosol dispersion performance with an FDI-approved human DPI device (Neohaler) correlated rate. In

Язык: Английский

Процитировано

2