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.

Autor: Kira AY; Department of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt. Electronic address: Ahmed.kira@deltauniv.edu.eg., Elmorsy EA; Department of Pharmacology and Therapeutics, College of Medicine, Qassim University, Buraidah 51452, Saudi Arabia. Electronic address: a.almarsa@qu.edu.sa., Hamad RS; Biological Sciences Department, College of Science, King Faisal University, Al Ahsa 31982, Saudi Arabia; Central Laboratory, Theodor Bilharz Research Institute, Giza 12411, Egypt. Electronic address: rhamad@kfu.edu.sa., Abdel-Reheim MA; Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia. Electronic address: m.ahmed@su.edu.sa., Elhemely MA; School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M20 4BX, UK; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef 62521, Egypt. Electronic address: mai.ali@manchester.ac.uk., El Adle Khalaf N; Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt. Electronic address: nouraeladle@mans.edu.eg., El-Kott AF; Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia; Department of Zoology, Faculty of Science, Damanhour University, Egypt. Electronic address: elkottaf@kku.edu.sa., AlShehri MA; Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia. Electronic address: mshehri@kku.edu.sa., Morsy K; Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia; Department of Zoology, Faculty of Science, Cairo University, Cairo, Egypt. Electronic address: kareemsaid156@yahoo.com., Negm S; Department of Life Sciences, College of Science and Art Mahyel Aseer, King Khalid University, Abha 62529, Saudi Arabia. Electronic address: snsir@kku.edu.sa., Mourad AAE; Pharmacology and Toxicology Department, Faculty of Pharmacy, Port-Said University, Port-Said 42511, Egypt. Electronic address: ahmed.mourad@pharm.psu.edu.eg., Ramadan A; Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt. Electronic address: Asmaa.esmail@deltauniv.edu.eg., Saber S; Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt. Electronic address: Sameh.saber@deltauniv.edu.eg.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Nov 15; Vol. 141, pp. 113000. Date of Electronic Publication: 2024 Aug 27.
DOI: 10.1016/j.intimp.2024.113000
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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