1. 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.
- Author
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Kira AY, Elmorsy EA, Hamad RS, Abdel-Reheim MA, Elhemely MA, El Adle Khalaf N, El-Kott AF, AlShehri MA, Morsy K, Negm S, Mourad AAE, Ramadan A, and Saber S
- Subjects
- Animals, Male, Rats, Liver drug effects, Liver metabolism, Liver pathology, Calcium Channel Blockers therapeutic use, Calcium Channel Blockers pharmacology, Calcium Channel Blockers administration & dosage, Rats, Sprague-Dawley, Anti-Inflammatory Agents therapeutic use, Anti-Inflammatory Agents pharmacology, Tissue Distribution, Chitosan chemistry, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Nanoparticles chemistry, NF-kappa B metabolism, Interleukin-1beta metabolism, Thioacetamide, Nicardipine therapeutic use, Nicardipine administration & dosage, Nicardipine pharmacology, Signal Transduction drug effects, Chemical and Drug Induced Liver Injury drug therapy
- 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., 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.)
- Published
- 2024
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