Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, 450003, Zhengzhou, China.
PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-Sen University, 510275, Guangzhou, China.
J Nanobiotechnology. 2021 Oct 26;19(1):341. doi: 10.1186/s12951-021-01079-w.
Effectively promoting corneal allograft survival remains a challenge in corneal transplantation. The emerging therapeutic agents with high pharmacological activities and their appropriate administration routes provide attractive solutions. In the present study, a celastrol-loaded positive nanomedicine (CPNM) was developed to enhance corneal penetration and to promote corneal allograft survival. The in vitro, in vivo and ex vivo results demonstrated the good performance of CPNM prolonging the retention time on ocular surface and opening the tight junction in cornea, which resulted in enhanced corneal permeability of celastrol. Both in vitro and in vivo results demonstrated that celastrol inhibited the recruitment of M1 macrophage and the expression of TLR4 in corneal allografts through the TLR4/MyD88/NF-κB pathway, thereby significantly decreasing secretion of multiple pro-inflammatory cytokines to promote corneal allograft survival. This is the first celastrol-based topical instillation against corneal allograft rejection to provide treatment more potent than conventional eye drops for ocular anterior segment diseases.
有效促进角膜同种异体移植物存活仍然是角膜移植中的一个挑战。具有高药理活性的新兴治疗药物及其适当的给药途径提供了有吸引力的解决方案。在本研究中，开发了一种载姜黄素的正纳米药物（CPNM），以增强角膜穿透性并促进角膜同种异体移植物存活。体外、体内和离体结果表明，CPNM 具有良好的性能，可以延长在眼表面的保留时间并打开角膜中的紧密连接，从而增强姜黄素的角膜通透性。体外和体内结果均表明，姜黄素通过 TLR4/MyD88/NF-κB 通路抑制角膜同种异体移植物中 M1 巨噬细胞的募集和 TLR4 的表达，从而显著减少多种促炎细胞因子的分泌，促进角膜同种异体移植物存活。这是首例基于姜黄素的局部滴眼剂用于对抗角膜同种异体排斥反应，为眼部前段疾病提供了比传统眼药水更有效的治疗方法。
