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聚乙二醇-二硫苏糖醇-硼酸水凝胶联合加替沙星靶向治疗细菌性角膜炎。

Targeted Bacterial Keratitis Treatment with Polyethylene Glycol-Dithiothreitol-Boric Acid Hydrogel and Gatifloxacin.

机构信息

Department of Ophthalmology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China.

出版信息

Curr Drug Deliv. 2024;21(11):1548-1558. doi: 10.2174/0115672018279105240226050253.

Abstract

INTRODUCTION/OBJECTIVE: To prolong the ocular residence time of gatifloxacin and enhance its efficacy against bacterial keratitis, this study developed a velocity-controlled polyethylene glycol-dithiothreitol-boric acid (PDB) hydrogel loaded with gatifloxacin.

METHODS

First, the basic properties of the synthesized PDB hydrogel and the gatifloxacin-loaded PDB hydrogel were assessed. Secondly, the degradation rate of the drug-loaded PDB was measured in a simulated body fluid environment with pH 7.4/5.5. The release behavior of the drug-loaded PDB was studied using a dialysis method with PBS solution of pH 7.4/5.5 as the release medium. Finally, a mouse model of bacterial keratitis was established, and tissue morphology was observed using hematoxylin-eosin staining. Additionally, mouse tear fluid was extracted to observe the antibacterial effect of the gatifloxacin-loaded PDB hydrogel.

RESULTS

The results showed that the PDB hydrogel had a particle size of 124.9 nm and a zeta potential of -23.3 mV, with good porosity, thermosensitivity, viscosity distribution, rheological properties, and high cell compatibility. The encapsulation of gatifloxacin did not alter the physical properties of the PDB hydrogel and maintained appropriate swelling and stability, with a high drug release rate in acidic conditions. Furthermore, animal experiments demonstrated that the gatifloxacin- loaded PDB hydrogel exhibited superior therapeutic effects compared to gatifloxacin eye drops and displayed strong antibacterial capabilities against bacterial keratitis.

CONCLUSION

This study successfully synthesized PDB hydrogel and developed a gatifloxacin drug release system. The hydrogel exhibited good thermosensitivity, pH responsiveness, stability, and excellent biocompatibility, which can enhance drug retention, utilization, and therapeutic effects on the ocular surface.

摘要

简介/目的:为了延长加替沙星的眼部滞留时间,增强其对细菌性角膜炎的疗效,本研究开发了一种载有加替沙星的速度控制型聚乙二醇-二硫苏糖醇-硼酸(PDB)水凝胶。

方法

首先,评估了合成的 PDB 水凝胶和载有加替沙星的 PDB 水凝胶的基本性质。其次,在 pH 值为 7.4/5.5 的模拟体液环境中测量了载药 PDB 的降解率。采用 pH 值为 7.4/5.5 的 PBS 溶液作为释放介质,通过透析法研究了载药 PDB 的释放行为。最后,建立了细菌性角膜炎小鼠模型,通过苏木精-伊红染色观察组织形态。此外,提取小鼠泪液观察载药 PDB 水凝胶的抑菌作用。

结果

结果表明,PDB 水凝胶粒径为 124.9nm,zeta 电位为-23.3mV,具有良好的孔隙率、温敏性、粘度分布、流变性能和高细胞相容性。载加替沙星不会改变 PDB 水凝胶的物理性质,保持适当的溶胀和稳定性,在酸性条件下具有较高的药物释放率。此外,动物实验表明,载药 PDB 水凝胶的治疗效果优于加替沙星滴眼液,对细菌性角膜炎具有较强的抗菌作用。

结论

本研究成功合成了 PDB 水凝胶,并开发了一种载加替沙星的药物释放系统。该水凝胶具有良好的温敏性、pH 响应性、稳定性和优良的生物相容性,能增强药物在眼表的滞留、利用和治疗效果。

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