Silver Nanoparticles with Mebeverine in IBS Treatment: DFT Analysis, Spasmolytic, and Anti-Inflammatory Effects

Abstract

Background/Objectives: 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. Methods: The interactions of AgNPs with cholinergic inhibitors, selective antagonists, Ca²⁺ 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. Results: 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. Conclusions: 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.

Keywords: HepG2 cells; anti-inflammatory activity; drug delivery (DD); gastrointestinal inflammation (GI); inflammatory bowel disease (IBD); mebeverine hydrochloride (MBH); molecular docking; silver nanoparticles; spasmolytic.

Figure 1

Chemical structure of mebeverine hydrochloride (MBH).

Figure 2

TEM visualization of drug-loaded silver nanoparticles with MBH.

Figure 3

Optimized geometries and obtained energy differences between six combinations of the two most stable ring forms of fructose in solution (in kcal mol⁻¹). The five-membered cycle is denoted as f, whereas the six-membered ring is denoted as p.

Figure 4

Adsorption energies and enthalpies of MBH/AgNP complex formation (in kcal mol⁻¹) for the drug in the [A] neutral form and the [B] cationic form. The structures are optimized at the B3LYP/6-311++G(d,p) level.

Figure 5

Changes in main parameters of spontaneous contractile activity: muscle tonus (mN), amplitude (mN), and frequency (n/min) under the influence of: (a) MBH; (b) AgNPs with MBH.

Figure 6

Inhibition of albumin’s thermal denaturation by MBH and drug-loaded AgNPs (%); * p < 0.05.

Figure 7

Inhibition of thermal denaturation of albumin by MBH (grey) and AgNPs with MBH (blue). The anti-inflammatory activity of the tested substances was compared to diclofenac’s and acetylsalicylic acid (ASA)’s activity (orange). The results are expressed as IC₅₀, mg/mL. ^# p < 0.05 compared to diclofenac; * p < 0.05 compared to ASA.

Figure 8

Microphotographs of SM preparations from the rat corpus incubated with MBH and MBH-loaded AgNPs for 1 h. (A) Control stained for IL-1β (black arrow), ×200. (B) Control stained for 5HT3 (black arrow), ×200. (C) SMs incubated with MBH showed the increased expression of IL-1β in the myenteric plexus (black arrow), ×200. (E) SMs incubated with AgNPs with MBH showed the weak expression of IL-1β in the myenteric plexus (black arrow), ×200. (D) SMs incubated with MBH, weakly stained cells in the myenteric plexus for 5HT3 (black arrow), ×200. (F) SMs incubated with AgNPs with MBH showed the weak expression of 5HT3 in the myenteric plexus (black arrow), ×200.

Figure 9

Effects of MBH, AgNPs, and their combination on HepG2 cell morphology and granularity at 24 h (A) and 72 h (B), assessed by FACS.

Figure 10

Effects of MBH, AgNPs, and their combination on HepG2 cell cycle at 24 h (A) and 72 h (B), assessed by FACS.

Figure 11

Drug-release concentrations for drug-loaded Ag NPs.