机构:[1]College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, China.[2]Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.[3]Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.四川大学华西医院
The topically administered glaucoma medications usually encounter serious precorneal drug loss and low corneal penetration, leading to a low bioavailability. In addition, due to the complexity of glaucoma etiology, a single medication is often insufficient. In this work, we report a novel dendritic oligoethylenimine decorated liposome for codelivery of two antiglaucoma drugs, latanoprost and timolol. The liposome showed a uniform nanoscopic particle size, positive surface charge, and excellent dual-drug loading capacity. A prolonged precorneal retention is observed by using this liposomal delivery system. This liposomal delivery system presents increased cellular uptake and tight junctions opening capacity, contributing respectively to the transcellular and paracellular permeation, thereby enhancing the trans-corneal transportation. Following topical administration of one eye drop in brown Norway rats, the dual-drug-loaded liposome formulation resulted in a sustained and effective intraocular pressure reduction as long as 5 days, without inducing ocular inflammation, discomfort, and tissue damage.
基金:
This work was supported by the National Natural Science
Foundation of China (52103177) and Natural Science
Foundation of Sichuan Province (2023MSFSC1000) (JW),
the Fundamental Research Funds for the Central Universities
(3332021106, 2019PT320028) and CAMS Innovation Fund
for Medical Sciences (2022-I2M-1-023) (BL), and the Science
& Technology Department of Sichuan Province (China)
funding project (No. 2021YFS0221 & 2023YFS0179) (JT).