Effectively inhibiting subconjunctival fibrosis remains a challenge in pterygium and antiglaucoma surgery. As one of the superior first-line clinical drugs, 5-fluorouracil (5-FU) possesses certain disadvantages, such as fast drug metabolism and poor dose controllability. The emergence of appropriate pharmaceutical formulation and administration routes provides attractive solutions. In this work, we report the development of a multilevel drug release strategy using two types of nature-derived biomaterials (biocompatible chitosan and silk protein) processed into nanofibers of different size ranges, which was shown to achieve sustained release of 5-FU, toward the unique application of inhibiting subconjunctival fibrosis. In vitro data demonstrated that this system achieved fast 5-FU release during the first 25 days, where the release became relatively stable and lengthy (3 months) afterward. More importantly, the in vivo outcomes also suggested a continuous long-lasting inhibitory effect on subconjunctival myofibroblasts. These results indicated that our nature-derived bionanomaterials served as a promising drug-carrying platform for inhibiting subconjunctival fibrosis by providing sustained release of pharmaceutical compounds thus reducing the administration frequency, which may find broad utility in the treatment of ocular diseases and possibly other biomedical applications.

有效抑制结膜下纤维化仍然是翼状胬肉和抗青光眼手术中的一个挑战。5-氟尿嘧啶（5-FU）作为临床一线用药的优势之一，具有药物代谢快、剂量可控性差等缺点。合适的药物制剂和给药途径的出现提供了有吸引力的解决方案。在这项工作中，我们报告了使用两种类型的天然衍生生物材料（生物相容性壳聚糖和丝蛋白）加工成不同尺寸范围的纳米纤维的多级药物释放策略的开发，这些材料被证明可以实现 5-FU 的持续释放，朝向抑制结膜下纤维化的独特应用。体外数据表明，该系统在前 25 天内实现了 5-FU 的快速释放，之后释放变得相对稳定和漫长（3 个月）。更重要的是，体内结果还表明对结膜下肌成纤维细胞具有持续持久的抑制作用。这些结果表明，我们的天然生物纳米材料通过提供药物化合物的持续释放从而降低给药频率，成为抑制结膜下纤维化的有前途的载药平台，这可能在治疗眼部疾病和其他生物医学应用中具有广泛的用途.