Multiloaded drug delivery devices for the treatment of glaucoma

Abstract

(rociohv@ucm.es)Glaucoma is a leading cause of blindness worldwide. In this neurodegenerative disease, a progressive death of retinal ganglion cells (RGC) and a glaucomatous optic disc neuropathy occurs which lead to visual impairment. Increase of Intraocular pressure (IOP) is a major risk factor strongly associated with retinal degeneration although a non IOP‐dependent neurodegeneration also occurs. Neurodegeneration process observed in glaucoma and other chronic retinal diseases occurs through different pathways: glutamate‐induced RGC cytotoxicity, apoptosis, neurotrophic factors deprivation, oxidative stress, calcium channel alteration and inflammation, among others. Due to the multifactorial character of the disease there is special interest in designing treatments able to include a combination of active agents in the same formulation. Unlike treatment to control IOP, which acts on the anterior segment of the eye and it can be administered topically, the applicability of neuroprotective therapies requires the administration of the active substances near to the retinal tissues using intraocular injections. Furthermore, due to the chronicity of the disease frequents administrations are required to reach and maintain therapeutic concentrations in the target site.Intraocular drug delivery systems are able to provide effective concentrations inside the eye for long term, thus reducing the number of interventions. Among the controlled release devices, implants (>1 mm) and microparticles (1–1000 μm), are capable of releasing the active substance in the vicinity of the retina for extended periods of time. Furthermore, if they are prepared with biodegradable polymers as the case of poly‐(lactic‐co‐glycolic) (PLGA), they have the advantage of disappearing from the site of administration after releasing the drug. Moreover, the final products of these biodegradable biomaterials result well tolerated and are finally eliminated from the body. Among the intraocular drug delivery devices, microspheres present a lot of advantages as they can be administered as a suspension in the vitreous using small gauge needles (30‐32G) without the need to surgery or stitches, which is more comfortable for ophthalmologists and patients, also reducing the risk of infection. Microspheres can be loaded with different agents that can be delivered simultaneously during long term. Another interesting advantage of microspheres is that, by being able to easily modify the amount of microparticles to be administered, they become very useful tools for personalized therapies. Thus, with these microsystems the number of administrations could be considerably reduced, spacing them even several months.Bravo‐Osuna I., Andrés‐Guerrero V., Arranz‐Romera A., Esteban‐Pérez S., Molina‐Martínez I.T., Herrero‐Vanrell R. Microspheres as intraocular therapeutic tools in chronic diseases of the optic nerve and retina. (2018) Advanced drug delivery reviews 126, 127–144.Acknowledgments: Grants PID2020‐113281RB‐C21 and PID2020‐113281RB‐C22 funded by MCIN/AEI/ 10.13039/501100011033; N° 813440 (ORBITAL– Ocular Research by Integrated Training and Learning).