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

IF 3.4 4区 医学 Q2 PHARMACOLOGY & PHARMACY AAPS PharmSciTech Pub Date : 2024-10-23 DOI:10.1208/s12249-024-02969-6
Mohammad Mohammadi, Shokoufeh Rahmani, Zohre Ebrahimi, Ghazal Nowroozi, Fatemeh Mahmoudi, Mohsen Shahlaei, Sajad Moradi
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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.

Graphical Abstract

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用抗生素负载介孔二氧化硅纳米粒子增强的原位形成水凝胶用于治疗细菌性角膜炎
细菌性角膜炎(BK)是一种严重的眼部感染,如不及时治疗可导致视力受损或失明。在此,我们报告了一种多功能复合水凝胶的开发情况,这种水凝胶由丝纤维素和海藻酸钠组成,并由装载抗生素的介孔二氧化硅纳米粒子(MSNs)增强,用于治疗 BK。该给药系统是通过在水凝胶网络中加入万古霉素和头孢他啶MSN而构建的。合成的 MSN 呈球形,平均尺寸约为 95 nm。万古霉素和头孢他啶的载药量分别约为 45% 和 43%。此外,该制剂还具有持续释放特性,在 24 小时内可释放 92% 的万古霉素和 90% 的头孢他啶。MTT 检测结果也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 的相互作用。从 RMSD、接触数和 MSD 分析中得到的结果完美地证实了实验结果。简而言之,所设计的药物-MSN@水凝胶将为 BK 的治疗揭开新的篇章。
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来源期刊
AAPS PharmSciTech
AAPS PharmSciTech 医学-药学
CiteScore
6.80
自引率
3.00%
发文量
264
审稿时长
2.4 months
期刊介绍: AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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