article · Journal of Controlled Release
Current treatments for neovascular retinal diseases rely on frequent eye injections because existing drug carriers cannot adapt their release rates to individual patient conditions. To address this, a responsive drug delivery platform was created using mesoporous silica nanoparticles designed to release humanin peptide in the presence of reactive oxygen species. The nanoparticles provide a high drug-loading capacity. In tests on bovine eye tissue, the particles remained immobilised in the vitreous under normal conditions but reversed their surface charge and diffused rapidly when exposed to oxidative stress. In cell experiments, retinal pigment epithelial cells internalised the particles, which released the peptide and prevented cell death caused by oxidative stress. Furthermore, tests in a mouse model of oxygen-induced retinopathy confirmed that the system effectively suppressed abnormal retinal blood vessel formation.
Neovascular retinal conditions often require repeated, invasive eye injections that place a heavy burden on patients and healthcare providers. By releasing medication only when triggered by disease-related oxidative stress, responsive nanoparticles could reduce injection frequency and provide targeted protection against retinal damage, helping to preserve vision more effectively over time.
This technology could enable responsive ocular therapies for neovascular retinal diseases, targeting pharmaceutical developers and ophthalmology clinics. Based on the abstract, the research is at an early experimental stage, having demonstrated proof of concept in cell cultures, ex vivo bovine eyes, and a mouse model.
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Intravitreal injection of biodegradable implant drug carriers shows promise in reducing the injection frequency for neovascular retinal diseases. However, current intravitreal ocular devices have limitations in adjusting drug release rates for individual patients, thereby affecting treatment effectiveness. Accordingly, we developed mesoporous silica nanoparticles (MSNs) featuring a surface that reverse its charge in response to reactive oxygen species (ROS) for efficient delivery of humanin peptide (HN) to retinal epithelial cells (ARPE-19). The MSN core, designed with a pore size of 2.8 nm, ensures a high HN loading capacity 64.4% (w/w). We fine-tuned the external surface of the MSNs by incorporating 20% Acetyl-L-arginine (Ar) to create a partial positive charge, while 80% conjugated thioketal (TK) methoxy polyethylene glycol (mPEG) act as ROS gatekeeper. Ex vivo experiments using bovine eyes revealed the immobilization of Ar-MSNs-TK-PEG (mean zeta potential: 2 mV) in the negatively charged vitreous. However, oxidative stress reversed the surface charge to -25 mV by mPEG loss, facilitating the diffusion of the nanoparticles impeded with HN. In vitro studies showed that ARPE-19 cells effectively internalize HN-loaded Ar-MSNs-TK, subsequently releasing the peptide, which offered protection against oxidative stress-induced apoptosis, as evidenced by reduced TUNEL and caspase3 activation. The inhibition of retinal neovascularization was further validated in an in vivo oxygen-induced retinopathy (OIR) mouse model.
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DOI: 10.1016/j.jconrel.2024.07.022
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