Yuhan Huang,1,* Dan Yan,1,* Weijie Ouyang,1,2,* Jiaoyue Hu,1,3 Zuguo Liu1,3,4 

1Xiamen University Affiliated Xiamen Eye Center; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science; Fujian Engineering and Research Center of Eye Regenerative Medicine; Eye Institute of Xiamen University; School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3Department of Ophthalmology, Xiang’an Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 4Department of Ophthalmology, The First Affiliated Hospital of University of South China, Hengyang, Hunan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zuguo Liu, Eye Institute of Xiamen University, 168 Daxue Road, Xiamen, Fujian, People’s Republic of China, Email zuguoliu@xmu.edu.cn Jiaoyue Hu, Eye Institute of Xiamen University, 168 Daxue Road, Xiamen, Fujian, People’s Republic of China, Email mydear_22000@163.com

Abstract: Ocular diseases present unique therapeutic challenges due to the complex anatomical and physiological barriers of the eye. Conventional drug delivery systems often suffer from poor bioavailability, rapid clearance, and inadequate targeting, limiting their clinical efficacy. Recent advances in smart nano-in-micro (NIM) platforms have emerged as a transformative strategy, combining the precision of nanoscale drug carriers with the stability and sustained-release capabilities of microscale matrices. These hierarchical systems enable enhanced drug penetration, prolonged retention, and targeted delivery to both anterior and posterior ocular segments. This review highlights the latest developments in NIM platforms, focusing on material innovations that optimize drug loading, release kinetics, and biocompatibility. The shared physicochemical properties of nano-micro particles that influence their performance across different administration routes (topical, intravitreal, subconjunctival), supported by mechanistic insights into their interactions with ocular tissues are discussed. By bridging nanoscale engineering with clinical ophthalmology, NIM platforms represent a paradigm shift in ocular therapeutics, offering the potential to revolutionize treatment for previously intractable eye diseases.

Keywords: nano-in-micro, nanoparticles, ocular diseases, ocular drug delivery