Oz Yavuz, Zheng Yuting, Kumar Prince, Kumar Lal Krishan, Roy Arpita, Qi Iris, Liu Zhanpeng Jim, Singh Pawan Kumar, Annabi Nasim
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California, Los Angeles 90095, United States.
Department of Ophthalmology, Mason Eye Institute, University of Missouri School of Medicine, Columbia, Missouri 65201, United States.
ACS Nano. 2025 Aug 5;19(30):27173-27191. doi: 10.1021/acsnano.5c02002. Epub 2025 Jul 23.
Mucoadhesive nanoparticles show promise for mucosal drug delivery, but ocular applications remain limited by rapid clearance, poor retention, and insufficient drug encapsulation. Existing systems struggle to deliver a full spectrum of therapeutics, hydrophobic drugs, hydrophilic drugs, and proteins, despite the critical need for such versatility in treating complex ocular diseases. Many eye conditions, including infection, inflammation, and degenerative disorder, require combination therapies or multidrug regimens for optimal therapeutic outcomes. To address these limitations, we developed a biocompatible tannic acid (TA)-cross-linked nanogel (NG) platform with robust mucoadhesion, anti-inflammatory, reactive oxygen species (ROS) scavenging properties, and sustained drug-release capabilities. The NGs were synthesized from a temperature-responsive poly(ethylene glycol)-based copolymer that self-aggregates above its lower critical solution temperature and is cross-linked with TA. TA's polyphenolic structure enables multimodal mucoadhesion and antioxidant activity, enhancing ocular retention and protecting against ROS-induced damage. The NGs achieved high loading efficiency (>80%) for diverse therapeutics, including moxifloxacin, a hydrophilic antibiotic; dexamethasone (Dex), a hydrophobic anti-inflammatory drug; as well as bovine serum albumin, used as a model protein to explore potential for protein encapsulation. In proof-of-concept studies, Dex-loaded NGs demonstrated sustained release (>24 days) and therapeutic efficacy and . Blank NGs also exhibited anti-inflammatory activity , comparable to Dex-loaded NGs in an acute model of ocular inflammation, demonstrating their intrinsic therapeutic potential. By enabling delivery of multiple therapeutic classes while providing inherent anti-inflammatory function, this TA-cross-linked NG platform offers a versatile and effective strategy for managing complex ocular diseases.
黏膜黏附纳米颗粒在黏膜给药方面显示出前景，但眼部应用仍受到快速清除、滞留性差和药物包封不足的限制。现有系统难以递送全谱治疗药物，包括疏水药物、亲水药物和蛋白质，尽管在治疗复杂眼部疾病时迫切需要这种多功能性。许多眼部疾病，包括感染、炎症和退行性疾病，需要联合治疗或多药方案以实现最佳治疗效果。为了解决这些限制，我们开发了一种生物相容性单宁酸（TA）交联纳米凝胶（NG）平台，该平台具有强大的黏膜黏附性、抗炎性、活性氧（ROS）清除特性和持续药物释放能力。NG由基于温度响应性聚乙二醇的共聚物合成，该共聚物在其较低临界溶液温度以上自聚集并与TA交联。TA的多酚结构实现了多模式黏膜黏附及抗氧化活性，增强了眼部滞留并防止ROS诱导的损伤。NG对多种治疗药物实现了高负载效率（>80%），包括亲水性抗生素莫西沙星；疏水性抗炎药物地塞米松（Dex）；以及用作模型蛋白以探索蛋白包封潜力的牛血清白蛋白。在概念验证研究中，载有Dex的NG表现出持续释放（>24天）及治疗效果。空白NG也表现出抗炎活性，在急性眼部炎症模型中与载有Dex的NG相当，证明了其内在治疗潜力。通过能够递送多种治疗类别同时提供固有抗炎功能，这种TA交联的NG平台为管理复杂眼部疾病提供了一种通用且有效的策略。
