Eyedrop-based macromolecular ophthalmic drug delivery for ocular fundus disease treatment

Abstract

Therapeutic antibodies are extensively used to treat fundus diseases by intravitreal injection, as eyedrop formulation has been rather challenging due to the presence of ocular barriers. Here, an innovative penetrating carrier was developed for antibody delivery in eyedrop formulations. We found that fluorocarbon-modified chitosan (FCS) would self-assemble with proteins to form nanocomplexes, which could effectively pass across the complicated ocular structure to reach the posterior eye segments in both mice and rabbits. In a choroidal melanoma–bearing mouse model, eyedrops containing FCS/anti-PDL1 could induce stronger antitumor immune responses than those triggered by intravenous injection of anti-PDL1. Moreover, in choroidal neovascularization–bearing mouse and rabbit models, FCS/anti-VEGFA eyedrops effectively inhibited vascular proliferation, achieving comparable therapeutic responses to those observed with intravitreal injection of anti-VEGFA. Our work presents an effective delivery carrier to treat fundus diseases using eyedrop of therapeutic proteins, which may enable at-home treatment of many eye diseases with great patient compliance.

Noninvasive Framework Nucleic Acid Eye Drops for Retinal Administration

“…(II) Alternatively, following topical administration, these nanostructures navigate through the interstices between the cornea and the conjunctiva, breach the sclera and choroid layers, and ultimately reach the retina (Figure ). Given the considerable anatomical distance from the cornea to the retina, as well as prior studies indicating that negatively charged entities, such as DNA, favor scleral penetration, and the inverse correlation between molecular size and scleral permeability, , we propose that the 20 bp DNA nanostructures are more likely to access the retina via the second pathway. Certainly, the empirical validation of these speculative mechanisms remains a requisite for future studies.…”

Nano-based ocular drug delivery systems: an insight into the preclinical/clinical studies and their potential in the treatment of posterior ocular diseases

“…Recently, a lot of nano-based drug delivery systems have been developed to overcome the limitations of conventional eye drops and deliver drugs to the retina. 37–63 These advanced delivery systems have shown promising outcomes in the ocular disease models both in vitro and in vivo by increasing the retention time of drugs on the cornea, enhancing drug penetration, or promoting drug delivery to the posterior segment of the eye through the corneal or conjunctival–scleral pathway. Herein, we provide a summary of preclinical research on novel nano-based drug delivery systems for topical delivery to the posterior segment of the eye in the recent five years (Table 3).…”

“…In both choroidal melanoma-bearing mouse model and choroidal neovascularization-bearing mouse/rabbit models, FCS/anti-programmed cell death ligand 1 (PDL1) or FCS/anti-VEGFA eyedrops showed excellent therapeutic outcomes, comparable to those with intravenous or intravitreal injections. 57…”

An immunotherapeutic artificial vitreous body hydrogel to control choroidal melanoma and preserve vision after vitrectomy

“…In vivo treatment of choroidal melanoma B16F10 or B16LS9 are two cell lines derived from murine cutaneous melanoma tissues and have been widely used to establish choroidal melanoma in previous studies (43)(44)(45). To establish the choroidal melanoma mouse model, 5 × 10 5 luciferase B16F10 cells were injected into the middle between the retina and choroid in the right eye of each mouse.…”