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载药介孔硅纳米颗粒原位形成水凝胶治疗细菌性角膜炎。

In Situ Forming Hydrogel Reinforced with Antibiotic-Loaded Mesoporous Silica Nanoparticles for the Treatment of Bacterial Keratitis.

机构信息

Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

AAPS PharmSciTech. 2024 Oct 23;25(8):254. doi: 10.1208/s12249-024-02969-6.

Abstract

Bacterial keratitis (BK) is a serious ocular infection that can lead to vision impairment or blindness if not treated promptly. Herein, we report the development of a versatile composite hydrogel consisting of silk fibroin and sodium alginate, reinforced by antibiotic-loaded mesoporous silica nanoparticles (MSNs) for the treatment of BK. The drug delivery system is constructed by incorporating vancomycin- and ceftazidime-loaded MSNs into the hydrogel network. The synthesized MSNs were found to be spherical in shape with an average size of about 95 nm. The loading capacities of both drugs were approximately 45% and 43%, for vancomycin and ceftazidime respectively. Moreover, the formulation exhibited a sustained release profile, with 92% of vancomycin and 90% of ceftazidime released over a 24 h period. The cytocompatibility of the drug carrier was also confirmed by MTT assay results. In addition, we performed molecular dynamics (MD) simulations to better reflect the drug-drug and drug-MSN interactions. The results obtained from RMSD, number of contacts, and MSD analyses perfectly corroborated the experimental findings. In brief, the designed drug-MSN@hydrogel could mark an intriguing new chapter in the treatment of BK.

摘要

细菌性角膜炎 (BK) 是一种严重的眼部感染,如果不及时治疗,可能导致视力损害或失明。在此,我们报告了一种多功能复合水凝胶的开发,该水凝胶由丝素蛋白和海藻酸钠组成,通过负载抗生素的介孔硅纳米粒子 (MSNs) 增强,用于治疗 BK。该药物递送系统通过将载万古霉素和头孢他啶的 MSNs 纳入水凝胶网络来构建。合成的 MSNs 呈球形,平均粒径约为 95nm。两种药物的载药量分别约为 45%和 43%,分别为万古霉素和头孢他啶。此外,该制剂表现出持续释放的特性,在 24 小时内释放了 92%的万古霉素和 90%的头孢他啶。通过 MTT 测定结果证实了药物载体的细胞相容性。此外,我们还进行了分子动力学 (MD) 模拟,以更好地反映药物-药物和药物-MSN 相互作用。RMSD、接触数和 MSD 分析的结果完全证实了实验结果。简而言之,设计的药物-MSN@水凝胶可能为 BK 的治疗开创一个激动人心的新篇章。

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