Purpose

Amoxicillin, a treatment option widely employed against H. pylori infection, is becoming ineffective due to the rising antimicrobial resistance. The poor stability of amoxicillin in gastric juice, as well as amoxicillin resistance in H. pylori, has a negative impact on amoxicillin’s therapeutic efficacy. Because of its metal chelating capacity, phytic acid has been shown to improve the antibacterial effectiveness of adjunct antimicrobials. Gastroretentive drug delivery carriers present a viable approach for treating gastric conditions owing to their higher gastric residence time and controlled drug release properties.

Methods

In the current investigation, amoxicillin and phytic acid loaded benzalkonium chloride (BAC) cross-linked pectin microparticles were prepared via ionic gelation technique with 83.65 ± 3.12% yield. Microparticles were evaluated based on drug release profile, drug degradation, permeation, mucoadhesion, β-lactamase inhibition, in vitro antimicrobial activity, in vivo gastro retention, in vivo gastroprotection and in vitro cytotoxicity parameters to ensure their therapeutic outcomes.

Results

In silico investigation predicted higher binding affinity (− 5.752 kcal/mol) of phytic acid with β-lactamase enzyme than clavulanic acid (− 4.870 kcal/mol). The microparticles that demonstrated 85.21 ± 1.12% entrapment efficiency and good mucoadhesive profile (~ 40%) showed high gastric stability and sustained release profile (~ 82% release in 14 h). SEM examination portrayed non-spherical particles with porous surfaces. FTIR and DSC analyses revealed no interaction between the drug and the polymer matrix. Microparticles were found to have superior β-lactamase inhibition potential and higher zone of inhibition (27.66 ± 2.49 mm)) compared with pure drug (18.33 ± 1.69). X-ray radiography study indicated that the prepared microparticles retained in the stomach for over 4 h.

Conclusion

In conclusion, provided with tremendous improvement in the drug’s stability in the gastric environment, these microparticles pose a viable option in the treatment of H. pylori infections.

Graphical Abstract

目的

阿莫西林是一种广泛用于治疗幽门螺杆菌感染的治疗选择，但由于抗菌药物耐药性的上升而变得无效。阿莫西林在胃液中的稳定性差，以及幽门螺杆菌对阿莫西林的耐药性，对阿莫西林的治疗效果产生负面影响。由于其金属螯合能力，植酸已被证明可以提高辅助抗菌剂的抗菌效果。胃滞留药物递送载体由于其较高的胃停留时间和受控药物释放特性而成为治疗胃部疾病的可行方法。

方法

在目前的研究中，通过离子凝胶技术制备了负载阿莫西林和植酸的苯扎氯铵（BAC）交联果胶微粒，产率为83.65±3.12%。根据药物释放曲线、药物降解、渗透、粘膜粘附、β-内酰胺酶抑制、体外抗菌活性、体内胃滞留、体内胃保护和体外细胞毒性参数对微粒进行评估，以确保其治疗效果。

结果

计算机研究预测植酸与 β-内酰胺酶的结合亲和力 (− 5.752 kcal/mol) 高于克拉维酸 (− 4.870 kcal/mol)。微粒具有 85.21 ± 1.12% 的包封率和良好的粘膜粘附特性​​ (~ 40%)，表现出较高的胃稳定性和持续释放特性（14 小时内释放~ 82%）。 SEM 检查描绘了具有多孔表面的非球形颗粒。 FTIR 和 DSC 分析表明药物和聚合物基质之间没有相互作用。与纯药物 (18.33 ± 1.69) 相比，微粒具有优异的 β-内酰胺酶抑制潜力和更高的抑制区 (27.66 ± 2.49 mm))。 X射线照相研究表明制备的微粒在胃中保留超过4小时。

结论

总之，这些微粒极大地改善了药物在胃环境中的稳定性，为治疗幽门螺杆菌感染提供了可行的选择。

图形概要