Stoyanova Mihaela, Milusheva Miglena, Gledacheva Vera, Todorova Mina, Kircheva Nikoleta, Angelova Silvia, Stefanova Iliyana, Pencheva Mina, Vasileva Bela, Hristova-Panusheva Kamelia, Krasteva Natalia, Miloshev George, Tumbarski Yulian, Georgieva Milena, Nikolova Stoyanka
Department of Organic Chemistry, Faculty of Chemistry, University of Plovdiv, 4000 Plovdiv, Bulgaria.
Department of Bioorganic Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria.
Pharmaceutics. 2025 Apr 24;17(5):561. doi: 10.3390/pharmaceutics17050561.
: Mebeverine hydrochloride (MBH) is an antispasmodic agent used to regulate bowel movements and relax intestinal smooth muscle, but its application is limited by specific side effects; therefore, this study investigates the effects of previously synthesized MBH-loaded silver nanoparticles (AgNPs) on smooth muscle contractile activity and their anti-inflammatory potential as an alternative delivery system. The interactions of AgNPs with cholinergic inhibitors, selective antagonists, Ca blockers, and key neurotransmitters were analyzed. In vitro, albumin denaturation suppression and ex vivo assays evaluated the anti-inflammatory effects of AgNPs-MBH, validated using a DFT in silico approach. To comprehensively assess the systemic impact and IBS treatment potential of AgNPs-MBH, we also examined in vitro their antimicrobial activity and hepatic cell responses, as the liver is a key organ in evaluating the overall safety and efficacy of nanoparticles. Additionally, the drug-release capabilities of Ag NPs were established. : Our findings indicate that AgNPs with MBH do not affect blocked cholinergic receptors, but their effects are more pronounced and distinct in amplitude and character than MBH. MBH-loaded AgNPs showed a lower anti-inflammatory effect than MBH but were still better than diclofenac. They also affected hepatic cell morphology and proliferation, suggesting potential for enhanced therapeutic efficacy. Drug-loaded AgNPs are considered not bactericidal. : Based on our results, drug-loaded AgNPs might be a promising medication delivery system for MBH and a useful treatment option for IBS. Future in vivo and preclinical experiments will contribute to the establishment of drug-loaded AgNPs in IBS treatment.
盐酸美贝维林（MBH）是一种用于调节肠道运动和松弛肠道平滑肌的解痉剂，但其应用受到特定副作用的限制；因此，本研究调查了先前合成的负载MBH的银纳米颗粒（AgNPs）对平滑肌收缩活性的影响及其作为替代递送系统的抗炎潜力。分析了AgNPs与胆碱能抑制剂、选择性拮抗剂、钙阻滞剂和关键神经递质的相互作用。在体外，白蛋白变性抑制和离体试验评估了AgNPs-MBH的抗炎作用，并使用密度泛函理论（DFT）计算机模拟方法进行了验证。为了全面评估AgNPs-MBH的全身影响和肠易激综合征（IBS）治疗潜力，我们还在体外检查了它们的抗菌活性和肝细胞反应，因为肝脏是评估纳米颗粒整体安全性和有效性的关键器官。此外，还确定了Ag NPs的药物释放能力。我们的研究结果表明，与MBH结合的AgNPs不会影响被阻断的胆碱能受体，但其作用在幅度和特征上比MBH更明显和独特。负载MBH的AgNPs的抗炎作用低于MBH，但仍优于双氯芬酸。它们还影响肝细胞形态和增殖，表明具有增强治疗效果的潜力。载药AgNPs被认为没有杀菌作用。基于我们的结果，载药AgNPs可能是一种有前途的MBH药物递送系统，也是IBS的一种有用治疗选择。未来的体内和临床前实验将有助于确定载药AgNPs在IBS治疗中的应用。
