Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, People's Republic of China.
NHC Key Laboratory of Myopia, Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, 200031, People's Republic of China.
Int J Nanomedicine. 2023 Jul 31;18:4347-4363. doi: 10.2147/IJN.S417750. eCollection 2023.
Autoimmune uveitis is a kind of sight-threatening ocular and systemic disorders. Recent treatments on autoimmune uveitis still remain many limitations due to extreme complexity and undetermined pathogenesis. In this study, a novel dual-drug nanocomposite formulation is developed to treat experimental autoimmune uveitis by a combined and sustained therapy method.
The dual-drug nanocomposite formulation is constructed by integrating berberine (BBR)-loaded mesoporous silica nanoparticles (MSNs) into dexamethasone (DEX)-loaded thermogel (BBR@MSN-DEX@Gel). The BBR@MSN-DEX@Gel is characterized by transmission electron microscopy, dynamic light scattering, Fourier transform infrared spectrometer and rheometer. The in vitro drug release profile, cytotoxicity and anti-inflammation effectiveness of BBR@MSN-DEX@Gel on lipopolysaccharide-stimulated human conjunctival epithelial cells are investigated. After the in vivo drug release profile and biosafety of the dual-drug nanocomposite formulation are confirmed, its treatment effectiveness is fully assessed based on the induced experimental autoimmune uveitis (EAU) Lewis rat's model.
The dual-drug nanocomposite formulation has good injectability and thermosensitivity, suitable for administration by an intravitreal injection. The BBR@MSN-DEX@Gel has been found to sustainably release both drugs for up to 4 weeks. The carrier materials have minimal in vitro cytotoxicity and high in vivo biosafety. BBR@MSN-DEX@Gel presents obviously anti-inflammatory effectiveness in vitro. After administration of BBR@MSN-DEX@Gel into Lewis rat's eye with EAU by an intravitreal injection, the nanocomposite formulation significantly suppresses inflammatory reaction of autoimmune uveitis via a dual-drug combined and sustained therapy method, compared with the equivalent dose of single-component formulations.
BBR@MSN-DEX@Gel serves as a promising dual-drug nanocomposite formulation for future treatment of autoimmune uveitis.
自身免疫性葡萄膜炎是一种威胁视力的眼内和全身疾病。由于发病机制极其复杂且不确定，目前针对自身免疫性葡萄膜炎的治疗方法仍存在许多局限性。在本研究中，通过联合和持续治疗方法，开发了一种新型的双药物纳米复合制剂来治疗实验性自身免疫性葡萄膜炎。
双药物纳米复合制剂是通过将载有黄连素（BBR）的介孔硅纳米粒子（MSNs）整合到载有地塞米松（DEX）的温敏凝胶（BBR@MSN-DEX@Gel）中构建而成。采用透射电子显微镜、动态光散射、傅里叶变换红外光谱仪和流变仪对 BBR@MSN-DEX@Gel 进行了表征。考察了 BBR@MSN-DEX@Gel 在脂多糖刺激的人结膜上皮细胞中的体外药物释放特性、细胞毒性和抗炎效果。在体内药物释放特性和双药物纳米复合制剂的生物安全性得到确认后，基于诱导的实验性自身免疫性葡萄膜炎（EAU）Lewis 大鼠模型，全面评估了其治疗效果。
双药物纳米复合制剂具有良好的可注射性和温敏性，适合通过玻璃体内注射给药。BBR@MSN-DEX@Gel 已被发现可持续释放两种药物长达 4 周。载体材料具有最小的体外细胞毒性和较高的体内生物安全性。BBR@MSN-DEX@Gel 在体外具有明显的抗炎作用。通过玻璃体内注射将 BBR@MSN-DEX@Gel 施用于 EAU Lewis 大鼠眼后，与单一组分制剂的等效剂量相比，纳米复合制剂通过双药物联合和持续治疗方法显著抑制了自身免疫性葡萄膜炎的炎症反应。
BBR@MSN-DEX@Gel 是一种很有前途的双药物纳米复合制剂，可用于未来治疗自身免疫性葡萄膜炎。
