To evaluate the safety of a novel nanoparticle neurotrophic factor complex for intraocular application in non-human primates.

Nanoparticles incorporated with ciliary neurotrophic factor (NP-CNTFs) were produced utilizing nanotechnology.Three adult male cynomolgus macaques were included and intravitreally injected with 10 μl NP-CNTFs at a concentration of 1 μg/μl into one of the two eyes, and these three eyes were designated as the NP-CNTFs group.The contralateral eyes received the same volume of phosphate buffered saline and were designated as the control group.Before the injection and on days 3 and 7 after the injection, routine clinical examinations of the anterior segment were performed to evaluate the ocular clinical symptoms such as conjunctival congestion, anterior chamber flare and cells.The fundus condition was observed by fundus photography.The morphological structure and thickness of retinas were detected by spectral domain-optical coherence tomography (SD-OCT).The use and care of animals were in accordance with the Guide for the Care and Use of Laboratory Animals issued by the National Institutes of Health and the standards of Association for Assessment and Accreditation of Laboratory Animal Care.The study protocol complied with the ethics of laboratory animal welfare and was approved by Hubei Topgene Biotechnology Co., Ltd.(No.IACUC-2019-012).

The NP-CNTFs prepared in this study had a particle size of (317±3)nm, a polydispersity index of 0.042±0.015, and a zeta potential of (-38.9±0.7)mV, and exhibited relatively good stability, bioavailability, and biocompatibility.Clinical examinations revealed that the clinical manifestations of conjunctival congestion, anterior chamber flare and cells were slightly more obvious in the NP-CNTFs group at 3 days after injection compared to the control group, but basically returned to normal at 7 days after injection.The scores of anterior-segment clinical symptoms of the NP-CNTFs and control group were (2.67±0.88) and (1.00±0.58) at 3 days after injection, and (0.67±0.33) and (0.33±0.33) at 7 days after injection, respectively, with no statistical differences between them (t=2.50, 1.00; both at P>0.05).Fundus photography showed normal fundus in both groups at 7 days after injection with no abnormal changes including vitreous opacity, vitreous hemorrhage, retinal hemorrhage or papilloedema.SD-OCT showed no significant histological changes in the retinas at 7 days after injection in both groups.The retinal nerve fiber layer thickness of the NP-CNTFs and control group were (107.67±0.88) and (111.00±3.22)μm, respectively, and the macular foveal thickness of the two groups were (255.67±2.03) and (254.67±3.84)μm, respectively, with no statistical differences between them (t=1.43, 0.50; both at P>0.05).

The complex NP-CNTFs shows good safety for intraocular application in cynomolgus macaques.

Nanoparticles; Ciliary neurotrophic factor; Cynomolgus macaques; Safety evaluation