State Key Laboratory of Precision Measurement Technology and Instrument, School of Precision Instruments & Opto-Electronics Engineering, Tianjin University, Tianjin 300072, China.
Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
J Mater Chem B. 2021 May 26;9(20):4190-4200. doi: 10.1039/d1tb00229e.
Eye-drop formulations as conventional regimens to tackle ocular diseases are far from efficient due to the rapid clearance by eye tears and the blockage of the corneal epithelium barrier. Here, we describe a bioadhesive glycosylated nanoplatform with boric acid pendants as a drug carrier for noninvasive trans-corneal delivery of drugs to treat corneal neovascularization (CNV), a serious corneal disease resulting in significant vision impairment. This biocompatible nanoplatform is formulated from a synthetic amphiphilic boric acid-based copolymer self-assembling to form highly stable micelles with a high loading capacity for dexamethasone (DEX). The nanoplatform is demonstrated to be in contact with the corneal epithelium for a long period under the bioadhesive function of boric acid modules and releases the drug over 96 h in a controlled manner. Our results also suggest that the nanoplatform can be efficiently internalized by corneal epithelial cells in vitro and realize transcytosis in vivo to greatly enhance the transcorneal penetration of the loaded drugs into the pathological corneal stroma. On topical application against rat corneal alkali burn, the nanoformulation presents more robust efficacy on neovascularization suppression and inflammation elimination than free DEX with a negligible effect on normal tissues. This bioadhesive strategy which focuses on extending ocular drug retention and improving trans-corneal drug delivery not only highlights an approach for alternative noninvasive therapy of CNV but also provides a versatile paradigm for other biomedical applications by overcoming protective barriers.
滴眼剂制剂作为传统方案来治疗眼部疾病的效果并不理想，因为它们会被眼内的泪液迅速清除，并且角膜上皮屏障会对其造成阻碍。在这里，我们描述了一种具有硼酸侧基的生物黏附性糖基化纳米平台，它可用作药物载体，通过非侵入性的经角膜途径将药物递送至角膜，以治疗角膜新生血管化（CNV），这是一种严重的角膜疾病，会导致显著的视力损伤。这种生物相容性纳米平台由一种合成的两亲性硼酸基共聚物组成，可自组装形成具有高载药量的高度稳定胶束，用于负载地塞米松（DEX）。研究表明，纳米平台在硼酸模块的生物黏附功能下可在角膜上皮上长时间接触，并以可控的方式在 96 小时内释放药物。我们的研究结果还表明，纳米平台可以在体外被角膜上皮细胞有效内化，并在体内实现转胞吞作用，从而极大地增强了负载药物进入病理性角膜基质的经角膜穿透性。在针对大鼠角膜碱烧伤的局部应用中，与游离 DEX 相比，纳米制剂在抑制新生血管形成和消除炎症方面表现出更强的疗效，对正常组织几乎没有影响。这种着眼于延长眼部药物滞留时间和改善经角膜药物递送的生物黏附策略，不仅为 CNV 的替代非侵入性治疗提供了一种方法，而且通过克服保护屏障，为其他生物医学应用提供了一种通用的范例。
