Novel formulations in the treatment of glaucoma
Authors: Vanrell Rocio Herrero 
Published: December 2022

Neuroprotective therapy in glaucoma is gaining a lot of interest to be used alone or simultaneously with the control of intraocular pressure (IOP). Neuronal degeneration process occurs through different pathways. For this reason, effective neuroprotection of retinal ganglion cells (RGC) and other retinal cells in glaucoma must be performed according to different targets. Recently, there is special interest in designing treatments able to include a combination of active agents in the same formulation.

Treatments destined to lower IOP, in which the target is the anterior segment of the eye are administered topically. By the contrary, neuroprotective therapies require the administration of the active substances close to the retinal tissues as well as their maintenance during long term. Since the last decades the development of intraocular drug delivery systems (IDDS) has emerged as therapeutic tools to provide therapeutic concentrations inside the eye during long term, thus reducing the number of injections. Among the controlled release devices, implants (>1 mm) and microparticles (1–1000 μm), are capable of releasing the active substance during long time. Furthermore, if they are prepared with biodegradable polymers, they have the advantage of disappearing from the site of administration after releasing the drug. There are currently two biodegradable implants in the clinical practice to avoid frequent administrations. One of them is loaded with dexamethasone (Ozurdex®) for intravitreal injection and Durysta™ administered in the anterior chamber. Both devices are prepared from the biopolymers derived from the lactic and glycolic acid poly‐(lactic‐co‐glycolic) acid, named as PLGA. The final products of this biodegradable biomaterial result well tolerated and they are finally eliminated from the body.

Despite the advantages of the commercialized biodegradable implants, they did not allow personalized therapy and microparticles (mainly PLGA microspheres) are under investigation as therapeutic platforms for intraocular purposes(1). One of their main advantages is that they can be administered as a suspension in the vitreous using small gauge needles (30‐32G). 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.

Microspheres allow to incorporate several drugs in the same device providing a simultaneous delivery of the active substances, resulting of special interest in multifactorial diseases(2). Furthermore, the amount of injected polymer in the co‐loaded device resulted lower compared to single‐loaded systems.

Acknowledgements‐Grant: PID2020‐113281RB‐C21 funded by MCIN/AEI/ 10.13039/501100011033, Research Group UCM 920415 “Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal)” and the ISCII‐FEDER RETICS (OFTARED) (RD16/0008/0004 and RD16/0008/0009).

References

1. Bravo‐Osuna I.; Andrés‐Guerrero V.; Arranz‐Romera A.; Esteban‐Pérez S.; Molina‐Martínez I.; Herrero‐Vanrell R. Microspheres as intraocular therapeutic tools in chronic diseases of the optic nerve and retina. Advanced Drug Delivery Reviews.2018. 126:127–144. DOI: 10.1016/j.addr.2018.01.007.

2. Arranz‐Romera A; Davis BM; Bravo‐Osuna I; Esteban‐Pérez S; Molina‐Martínez IT; Shamsher E; Ravindran N; Guo L; Cordeiro MF; Herrero‐Vanrell R. Simultaneous co‐delivery of neuroprotective drugs from multi‐loaded PLGA microspheres for the treatment of glaucoma. Journal of Controlled Release. 2019. 297:26–38. DOI: 10.1016/j.jconrel.2019.01.012.