Nicardipine-chitosan nanoparticles alleviate thioacetamide-induced acute liver injury by targeting NFκB/NLRP3/IL-1β signaling in rats: Unraveling new roles beyond calcium channel blocking

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Kira A.Y.; Elmorsy E.A.; Hamad R.S.; Abdel-Reheim M.A.; Elhemely M.A.; El Adle Khalaf N.; El-kott A.F.; AlShehri M.A.; Morsy K.; Negm S.; Mourad A.A.E.; Ramadan A.; Saber S.

Journal: International Immunopharmacology

Publisher: Elsevier B.V.

Publication Date: November 2024

Volume / Issue: Volume 141

Article No.: 113000

ISSN: 15675769

DOI: 10.1016/j.intimp.2024.113000

Scopus: View on Scopus

PubMed: 39191124

Document Type: Article

Authors and Affiliations

Kira A.Y., Department of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt; Elmorsy E.A., Department of Pharmacology and Therapeutics, College of Medicine, Qassim University, Buraidah, 51452, Saudi Arabia; Hamad R.S., Biological Sciences Department, College of Science, King Faisal University, Al Ahsa, 31982, Saudi Arabia, Central Laboratory, Theodor Bilharz Research Institute, Giza, 12411, Egypt; Abdel-Reheim M.A., Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra, 11961, Saudi Arabia; Elhemely M.A., School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M20 4BX, United Kingdom, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, 62521, Egypt; El Adle Khalaf N., Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt; El-kott A.F., Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia, Department of Zoology, Faculty of Science, Damanhour University, Egypt; AlShehri M.A., Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia; Morsy K., Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia, Department of Zoology, Faculty of Science, Cairo University, Cairo, Egypt; Negm S., Department of Life Sciences, College of Science and Art Mahyel Aseer, King Khalid University, Abha, 62529, Saudi Arabia; Mourad A.A.E., Pharmacology and Toxicology Department, Faculty of Pharmacy, Port-Said University, Port-Said, 42511, Egypt; Ramadan A., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt; Saber S., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt

Abstract

Liver inflammatory diseases are marked by serious complications. Notably, nicardipine (NCD) has demonstrated anti-inflammatory properties, but its benefits in liver inflammation have not been studied yet. However, the therapeutic efficacy of NCD is limited by its short half-life and low bioavailability. Therefore, we aimed to evaluate the potential of NCD-loaded chitosan nanoparticles (ChNPs) to improve its pharmacokinetic profile and hepatic accumulation. Four formulations of NCD-ChNPs were synthesized and characterized. The optimal formulation (NP2) exhibited a mean particle diameter of 172.6 ± 1.94 nm, a surface charge of +25.66 ± 0.93 mV, and an encapsulation efficiency of 88.86 ± 1.17 %. NP2 showed good physical stability as a lyophilized powder over three months. It displayed pH-sensitive release characteristics, releasing 77.15 ± 5.09 % of NCD at pH 6 (mimicking the inflammatory microenvironment) and 52.15 ± 3.65 % at pH 7.4, indicating targeted release in inflamed liver tissues. Pharmacokinetic and biodistribution studies revealed that NCD-ChNPs significantly prolonged NCD circulation time and enhanced its concentration in liver tissues compared to plain NCD. Additionally, the study investigated the protective effects of NCD-ChNPs in thioacetamide-induced liver injury in rats by modulating the NFκB/NLRP3/IL-1β signaling axis. NCD-ChNPs effectively inhibited NFκB activation, reduced NLRP3 inflammasome activation, and subsequent release of IL-1β, which correlated with improved hepatic function and reduced inflammation and oxidative stress. These findings highlight the potential of NCD-ChNPs as a promising nanomedicine strategy for the treatment of liver inflammatory diseases, warranting further investigation into their clinical applications, particularly in hypertensive patients with liver inflammatory conditions. © 2024

Keywords

Chitosan nanoparticles; Liver biodistribution; Liver inflammatory diseases; New therapeutic target; NFκB/NLRP3/IL-1β signaling; Nicardipine; Animals; Anti-Inflammatory Agents; Calcium Channel Blockers; Chemical and Drug Induced Liver Injury; Chitosan; Interleukin-1beta; Liver; Male; Nanoparticles; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley; Signal Transduction; Thioacetamide; Tissue Distribution; chitosan nanoparticle; cryopyrin; immunoglobulin enhancer binding protein; interleukin 1beta; organic solvent; tripolyphosphate; antiinflammatory agent; calcium channel blocking agent; IL1B protein, rat; nanoparticle; Nlrp3 protein, rat; analysis of variance; animal cell; animal experiment; animal model; animal tissue; Article; bleeding; controlled study; differential scanning calorimetry; dispersity; drug concentration; encapsulation; environmental temperature; enzyme linked immunosorbent assay; gelation; hepatitis; in vitro study; in vivo study; inflammatory cell; liver function; liver injury; liver tissue; nanopharmaceutics; network analysis; nonhuman; photon correlation spectroscopy; physical chemistry; post hoc analysis; rat; statistical analysis; stretching; surface charge; thermography; thioacetamide-induced hepatotoxicity; thioacetamide-induced liver injury; transmission electron microscopy; zeta potential; animal; chemistry; drug effect; drug therapy; metabolism; pathology; Sprague Dawley rat

Citation Information

Scopus Citations: 20

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