Nifuroxazide-loaded cubosomes exhibit an advancement in pulmonary delivery and attenuate bleomycin-induced lung fibrosis by regulating the STAT3 and NF-κB signaling: A new challenge for unmet therapeutic needs

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Saber S.; Nasr M.; Kaddah M.M.Y.; Mostafa-Hedeab G.; Cavalu S.; Mourad A.A.E.; Gaafar A.G.A.; Zaghlool S.S.; Saleh S.; Hafez M.M.; Girgis S.; Elgharabawy R.M.; Nader K.; Alsharidah M.; Batiha G.E.-S.; El-Ahwany E.; Amin N.A.; Elagamy H.I.; Shata A.; Nader R.; Khodir A.E.

Journal: Biomedicine and Pharmacotherapy

Publisher: Elsevier Masson s.r.l.

Publication Date: April 2022

Volume / Issue: Volume 148

Article No.: 112731

ISSN: 7533322

DOI: 10.1016/j.biopha.2022.112731

Scopus: View on Scopus

PubMed: 35220029

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Saber S., Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt; Nasr M., Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo, 11790, Egypt, Department of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Kaddah M.M.Y., Pharmaceutical and Fermentation Industries Development Center, City of Scientific Research and Technological Applications, Alexandria, New Borg El-Arab, 21934, Egypt; Mostafa-Hedeab G., Pharmacology Department & Health Research Unit, Medical College, Jouf University, Saudi Arabia, Pharmacology Department, Faculty of Medicine, Beni-Suef University, Beni Suef, Egypt; Cavalu S., Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, Oradea, 410087, Romania; Mourad A.A.E., Department of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University, Port Said, 42511, Egypt; Gaafar A.G.A., Department of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University, Port Said, 42511, Egypt; Zaghlool S.S., Pharmacology and Toxicology Department, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, 11571, Egypt; Saleh S., Department of Clinical Physiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt; Hafez M.M., Department of Biochemistry, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt; Girgis S., Department of Pharmaceutics, Faculty of Pharmacy, Alsalam University, Egypt; Elgharabawy R.M., Pharmacology and Toxicology Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt; Nader K., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt; Alsharidah M., Department of Physiology, College of Medicine, Qassim University, Qassim, 51452, Saudi Arabia; Batiha G.E.-S., Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, AlBeheira, Damanhour, 22511, Egypt; El-Ahwany E., Department of Immunology, Theodor Bilharz Research Institute, Giza, 12411, Egypt; Amin N.A., Department of Haematology, Theodor Bilharz Research Institute, Giza, 12411, Egypt; Elagamy H.I., Department of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Shata A., Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt, Department of Clinical Pharmacy, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Nader R., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt; Khodir A.E., Department of Pharmacology, Faculty of Pharmacy, Horus University, New Damietta, Egypt

Abstract

Pulmonary fibrosis (PF) is a chronic progressive disease that portends a very poor prognosis. It has been suggested that STAT3 is a potential target in PF. This study highlights the importance of cubosomes as a drug delivery system in enhancing the bioavailability of nifuroxazide (NXZD), a poorly soluble STAT3 inhibitor. NXZD-loaded cubosomes (NXZD-LC) were in vitro and in vivo evaluated. In vitro, cubosomes presented a poly-angular nanosized particles with a mean size and zeta potential of 223.73 ± 4.73 nm and − 20.93 ± 2.38 mV, respectively. The entrapment efficiency of nifuroxazide was 90.56 ± 4.25%. The in vivo pharmacokinetic study and the lung tissue accumulation of NXZD were performed by liquid chromatography-tandem mass spectrometry after oral administration to rats. The nanoparticles exhibited a two-fold increase and 1.33 times of bioavailability and lung tissue concentration of NXZD compared to NXZD dispersion, respectively. In view of this, NXZD-LC effectively attenuated PF by targeting STAT3 and NF-κB signals. As a result, NXZD-LC showed a potential anti-inflammatory effect as revealed by the significant decrease in MCP-1, ICAM-1, IL-6, and TNF-α and suppressed fibrogenic mediators as indicated by the significant reduction in TGF-β, TIMP-1, and PDGF-BB in lung tissues. Besides, NXZD-LC improved antioxidant defense mechanisms and decreased LDH and BALF total protein. These effects contributed to decreased collagen deposition. To conclude, cubosomes represent an advantageous pharmaceutical delivery system for enhancing pulmonary delivery of poorly soluble drugs. Additionally, repurposing NXZD as an antifibrotic agent is a promising challenge and new therapeutic approach for unmet therapeutic needs. © 2022 The Authors

Keywords

Bleomycin-induced lung fibrosis; Cubosomes; LC-MS/MS; NF-κB; Nifuroxazide; Pharmacokinetics; Pulmonary delivery; STAT3; Administration, Oral; Animals; Anti-Inflammatory Agents; Antifibrotic Agents; Biological Availability; Bleomycin; Drug Delivery Systems; Hydroxybenzoates; Lung; Male; Nanoparticles; NF-kappa B; Nitrofurans; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; Signal Transduction; STAT3 Transcription Factor; antifibrotic agent; antioxidant; collagen; cubosome; eosin; hematoxylin; hydroxyproline; immunoglobulin enhancer binding protein; intercellular adhesion molecule 1; interleukin 6; lactate dehydrogenase; malonaldehyde; monocyte chemotactic protein 1; nanoparticle; nitrate; nitrite; platelet derived growth factor BB; secobarbital; STAT3 protein; superoxide dismutase; tissue inhibitor of metalloproteinase 1; toll like receptor 4; transcription factor RelA; transforming growth factor beta; tumor necrosis factor; unclassified drug; antiinflammatory agent; hydroxybenzoic acid derivative; nitrofuran derivative; adult; animal experiment; animal model; animal tissue; antiinflammatory activity; area under the curve; Article; bicinchoninic acid assay; binding affinity; bioavailability; bleomycin-induced pulmonary fibrosis; bronchoalveolar lavage fluid; colorimetry; controlled study; drug delivery system; enzyme activity; enzyme linked immunosorbent assay; flow rate; histology; histopathology; leukocyte differential count; liquid chromatography-mass spectrometry; NF kB signaling; nonhuman; oxidative stress; particle size; protein content; quality control; rat; real time reverse transcription polymerase chain reaction; single drug dose; spectrophotometry; transmission electron microscopy; zeta potential; animal; chemistry; drug effect; lung fibrosis; metabolism; oral drug administration; pathology; pharmacology; procedures; Sprague Dawley rat

Citation Information

Scopus Citations: 28

For comprehensive information about the Theodor Bilharz Research Institute (TBRI), its institutional activities, scientific and research achievements, clinical and hospital services, and the diverse expertise offered through its 22 specialized research and clinical departments, as well as opportunities for professional training, specialized workshops, and scientific conferences, readers are invited to visit the Institute’s official website.

The website provides regularly updated information on the Institute’s latest news, research activities, scientific initiatives, clinical services, institutional programs, and academic and professional opportunities.

English Website: https://www.tbri.sci.eg/en/

Arabic Website: https://www.tbri.sci.eg/ar/

Prepared and Uploaded by:

Abdalla F. Abdalla

Electronic Portal Unit

Electronic Portal Unit

Popular Posts

A cost-performance index for nano-optical biosensor evaluation: Systematic evaluation of europium–salicylate luminescent platforms for GPC3-targeted early HCC diagnosis

Image
Bibliographic Information Authors: Hassan Y.M.; El-Tantawi H.; Ali I.R.; Attia M.S. Journal: Talanta Publisher: Elsevier B.V. Publication Date: January 2027 Volume / Issue: Volume 311 Article No.: 130103 ISSN: 399140 DOI: 10.1016/j.talanta.2026.130103 Scopus: View on Scopus PubMed: 42391698 Document Type: Review Authors and Affiliations Hassan Y.M., Department of Zoology, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt; El-Tantawi H., Department of Zoology, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt; Ali I.R., Department of Immunology and Treatment Evaluation, Theodore Bilharz Research Institute, Giza, Egypt; Attia M.S., Chemistry Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi Arabia Abstract Comparative evaluation of nano-optical biosensor platforms lacks a standardised, multi-parameter quantitative framework that integrates analytical performance...
Read more

Interpretation of liver stiffness measurement in patients with mixed liver disease etiologies

Image
Bibliographic Information Authors: El Ray A.; El Ghannam M.; Rautou P.E. Journal: Arab Journal of Gastroenterology Publisher: Elsevier Ltd Publication Date: August 2026 ISSN: 16871979 DOI: 10.1016/j.ajg.2026.05.002 Scopus: View on Scopus PubMed: 42362465 Document Type: Letter Authors and Affiliations El Ray A., Theodor Bilharz Research Institute, Hepatogastroenterology Department, Giza, Egypt, Faculty of Medicine, October 6 University, Egypt; El Ghannam M., Theodor Bilharz Research Institute, Hepatogastroenterology Department, Giza, Egypt; Rautou P.E., Université Paris-Cité, Inserm, Centre de recherche sur l’inflammation, UMR 1149, Paris, France, AP-HP, Hôpital Beaujon, Service d’Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France Abstract Vibration-controlled transient elastography (VCTE)–based liver stiffness measurement (LSM) is widely used for non-invasive assessment of liver fibrosis and p...
Read more

Holothuria arenicola Extract-Loaded Polycaprolactone Nanocapsules Attenuate Bile Duct Ligation-Induced Acute Liver Injury

Image
Bibliographic Information Authors: Mansour E.M.; Shemis M.; Fahmy S.R.; Amer M.A.; Mohamed A.S. Journal: Current Nanomedicine Publisher: Bentham Science Publishers Publication Date: September 2026 Volume / Issue: Volume 16 / Issue 5 Pages: 771–786 ISSN: 24681873 DOI: 10.2174/0124681873401484250924125945 Scopus: View on Scopus Document Type: Article Authors and Affiliations Mansour E.M., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt; Shemis M., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt; Fahmy S.R., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt; Amer M.A., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt; Mohamed A.S., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt Abstract Introduction: Cholestatic liver diseases are characterized by jaundice and cholestasis with various conseq...
Read more

Mytilus edulis-mediated green synthesis of selenium nanoparticles with antimicrobial and molluscicidal applications

Image
Bibliographic Information Authors: Dokmak H.-A.A.; AlSedawy M.; Ramadan M.A.; Amin B.H.; Faid A.H.; Abdelmaksoud H.F.; El-Sayed S.M. Journal: Scientific Reports Publisher: Nature Research Publication Date: 7 September 2026 Volume / Issue: Volume 16 / Issue 1 Article No.: 27918 ISSN: 20452322 DOI: 10.1038/s41598-026-65860-3 Scopus: View on Scopus PubMed: 42706305 Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Dokmak H.-A.A., Department of Medical Malacology, Theodor Bilharz Research Institute, Giza, Egypt; AlSedawy M., Microbiology and Immunology Department, Faculty of Pharmacy (For Boys), Al-Azhar University, Cairo, Egypt; Ramadan M.A., Department of Laser Application in Metrology, Photochemistry and Agriculture, National Institute of Laser Enhanced Science (NILES) Cairo University (CU), Giza, Egypt; Amin B.H., The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, 11787,...
Read more

Microbial levan potentiates hepatic retention and antitumor activity of a PEGylated benzimidazole–curcumin nanocomplex through TLR2–FXR/FGF15-associated immunometabolic remodeling in experimental liver cancer

Image
Bibliographic Information Authors: Shawky H.; Ibrahim N.E.; Amer M.N.; Al-Ashmawy A.A.K.; Hammam O.A.; Fayed D.B.; Maghraby A.S. Journal: Scientific Reports Publisher: Nature Research Publication Date: 12 August 2026 Volume / Issue: Volume 16 / Issue 1 Article No.: 25094 ISSN: 20452322 DOI: 10.1038/s41598-026-64576-8 Scopus: View on Scopus PubMed: 42581056 Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Shawky H., Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, 12622, Egypt; Ibrahim N.E., Microbial Biotechnology Department, Biotechnology Research Institute, National Research Centre, Dokki, Cairo, 12622, Egypt; Amer M.N., Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, 12622, Egypt; Al-Ashmawy A.A.K., Therapeutic Chem...
Read more

Variable clinical presentations of pulmonary hydatid cysts: a four-case series from a single center in United Arab Emirates, non-endemic region

Image
Bibliographic Information Authors: Yehya M.; Abdallah M.F.H.; Ajeka S.; Al-Masalmeh F.H.; Albaghdadi M.O.J. Journal: Journal of Surgical Case Reports Publisher: Oxford University Press Publication Date: 29 July 2026 Volume / Issue: Volume 2026 / Issue 7 Article No.: rjag658 ISSN: 20428812 DOI: 10.1093/jscr/rjag658 Scopus: View on Scopus Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Yehya M., Department of Thoracic Surgery, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates; Abdallah M.F.H., Department of Radiology, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates, Theodor Bilharz Research Institute, Mahad Al Abhas Al bahari St, Kornish Al Nile, Warraq Al Arab, Al Warak, Governorate, Giza, 3863341, Egypt; Ajeka S., Department of General Surgery, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates; Al-Masalmeh F.H., Department of ...
Read more

Corrigendum to ‘Eco-friendly approach for the removal and simultaneous detection of cyanide toxins from drinking and wastewater sources’ [Environ. Pollut. 385 (2025) 127094]

Image
Bibliographic Information Authors: El-Sewify I.M.; Shenashen M.A.; Gomaa H.; Selim M.S.; Akhtar N.; Azzam A.; Mekawy M.; Emran M.Y.; Khairy M.; Shahat A.; Hasan M.; Elmarakbi A.; El-Safty S.A. Journal: Environmental Pollution Publisher: Elsevier Ltd Publication Date: September 2026 Volume / Issue: Volume 405 Article No.: 128412 ISSN: 2697491 DOI: 10.1016/j.envpol.2026.128412 Scopus: View on Scopus PubMed: 42259729 Document Type: Erratum Authors and Affiliations El-Sewify I.M., Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1–2-1 Sengen, Ibaraki-ken, Tsukubashi, 305–0047, Japan, Chemistry Department, Faculty of Science, Ain Shams University, Abbasia, Cairo, 11566, Egypt; Shenashen M.A., Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1–2-1 Sengen, Ibaraki-ken, Tsukubashi, 305–0047, Japan; Gomaa H., Research Center for Macromolecules and Biomaterials, Na...
Read more