壳聚糖-青蒿琥酯纳米颗粒:预防青光眼滤过手术后水泡纤维化的双重抗纤维化和抗炎策略。

IF 5.5 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Drug Delivery and Translational Research Pub Date : 2025-10-01 Epub Date: 2025-02-28 DOI:10.1007/s13346-025-01819-7
Jingyuan Liu, Shutong Wang, Guangshuang Tan, Boding Tong, Ying Wu, Lusi Zhang, Bing Jiang
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引用次数: 0

摘要

青光眼滤过手术(GFS)可有效降低青光眼患者的眼压,但术后水泡纤维化常导致手术失败。青蒿琥酯(ART)已显示出抗纤维化的潜力;但其溶解性差、降解快,限制了其临床应用。本研究旨在开发壳聚糖-ART纳米颗粒(CS@ART NPs),以提高ART预防水泡纤维化的治疗效果。CS@ART NPs采用离子凝胶法制备壳聚糖包封。研究人员利用TEM、DLS、zeta电位分析、HPLC、FT-IR、1H-NMR和黏附试验等多种技术对其进行了表征,包括形貌、水动力学、表面电荷、包封效率、药物释放动力学、稳定性、化学结构和黏附相互作用分析。通过结膜下注射兔GFS模型评价其抗纤维化作用。采用组织学分析和免疫组化检测纤维化标志物α-SMA和纤维连接蛋白。体外研究采用TGF-β1刺激的人原代眼成纤维细胞,通过EdU掺入、Western blot检测信号通路成分和细胞因子表达来评估其抗炎和抗增殖作用。CS@ART NPs具有粒径分布均匀(135.73±0.90 nm)、分散稳定、包封率高(86.4%)、缓释等特点。在GFS模型中,单次结膜下注射CS@ART可显著减少胶原沉积,以及手术部位α-SMA和纤维连接蛋白的表达。在体外,CS@ART显示出优越的抗纤维化作用,与单独ART相比,其抑制成纤维细胞增殖的IC50显着降低。机械上,CS@ART抑制Cyclin D1-CDK4/6、TGF-β1/SMAD和PI3K/Akt信号通路。此外,CS@ART具有明显的抗炎作用,可降低炎症细胞浸润和IL-6的表达。CS@ART NPs在GFS后起到缓解水泡纤维化和炎症的双重作用,是改善青光眼患者手术结果的一种有希望的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chitosan-Artesunate nanoparticles: A dual anti-fibrotic and anti-inflammatory strategy for preventing bleb fibrosis post-glaucoma filtration surgery.

Glaucoma filtration surgery (GFS) effectively lowers intraocular pressure in glaucoma patients, but postoperative bleb fibrosis often leads to surgical failure. Artesunate (ART) has demonstrated antifibrotic potential; however, its clinical use is limited by poor solubility and rapid degradation. This study aimed to develop chitosan-ART nanoparticles (CS@ART NPs) to improve ART's therapeutic efficacy in preventing bleb fibrosis. CS@ART NPs were synthesized using an ionic gelation method for chitosan encapsulation. Their characterization, including analyses of morphology, hydrodynamic properties, surface charge, encapsulation efficiency, drug release kinetics, stability, chemical structure, and mucoadhesive interactions, was carried out using various techniques such as TEM, DLS, zeta potential analysis, HPLC, FT-IR, 1H-NMR, and adhesion assays. The antifibrotic effects were evaluated in a rabbit GFS model through subconjunctival injection. Histological analysis as well as immunohistochemistry for fibrosis markers α-SMA and fibronectin were detected. In vitro studies were conducted using human primary ocular fibroblasts stimulated with TGF-β1 to assess anti-inflammatory and anti-proliferative effects, measured by EdU incorporation, Western blot for signaling pathway components, and cytokine expression. CS@ART NPs exhibited a uniform size distribution (135.73 ± 0.90 nm), stable dispersion, high encapsulation efficiency (86.4%), and sustained drug release. In the GFS model, a single subconjunctival injection of CS@ART significantly reduced collagen deposition, as well as α-SMA and fibronectin expression at the surgical site. In vitro, CS@ART demonstrated superior antifibrotic effects with a significantly lower IC50 for inhibiting fibroblast proliferation compared to ART alone. Mechanically, CS@ART suppressed the Cyclin D1-CDK4/6, TGF-β1/SMAD, and PI3K/Akt signaling pathways. Additionally, CS@ART showed marked anti-inflammatory effects, reducing inflammatory cell infiltration and IL-6 expression. CS@ART NPs play a dual role both alleviate bleb fibrosis and inflammation after GFS as a promising therapeutic strategy for improving surgical outcomes in glaucoma patients.

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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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