Topical ocular administration of progesterone may be a viable treatment for retinitis pigmentosa

Retinitis pigmentosa is a degenerative disease affecting the photoreceptor cells of the retina, called cones and rods. Of genetic origin, this disease first affects vision in low light conditions, then progressively affects peripheral vision and the central visual field until total loss of sight, as cells die. photoreceptors. Noting recent research on the role of hormones, particularly progesterone, in preventing cell death due to oxidative stress, the CEU UCH Drug Delivery Systems (DDS) research group has developed and successfully tested a range of methods to administration of this hormone to the eye to slow down the degenerative process characteristic of retinitis pigmentosa.

The research undertaken by the team is detailed in Dr. Adrián Alambiaga’s doctoral thesis, directed by Professor Alicia López Castellano and Dr. Aracely Calatayud, and which he successfully defended at CEU in April. His findings, already published in several journals, show that progesterone can be delivered in various forms, such as eye drops, micelles and inserts, in sufficient quantity to penetrate the surface of the eye and reach the neuroretina without causing toxicity or significant irritation.

The use of ocular inserts makes it possible to deliver progesterone in greater quantities than when using aqueous solutions. Although we have seen that aqueous solutions can also permeate the sclera and cornea, the inserts performed best in our tests, as they release progesterone for uptake by the neuroretina over a longer and greater period of time. amount.”


Dr Adrian Alambiaga

Topical administration, the best option

Progesterone is practically insoluble in water and dissolves only slowly and incompletely in gastrointestinal fluids. This means that when taken orally, it quickly becomes ineffective. Also, high levels of progesterone must be taken orally so that only a small amount can reach the eye. “That’s why it was important to study the different ways to deliver progesterone topically or locally in the eye, thus limiting the amount to be administered.”

During his doctoral research, Dr. Alambiaga, under the guidance of Prof. López Castellano and Dr. Calatayud, developed a range of pharmaceutical formulations of progesterone for topical administration to the eye. These included aqueous solutions, which increase the durability and diffusion of molecules on the ocular surface, and ocular inserts, which increase the contact time of the drug on the ocular surface, increase the availability of the drug in the body and allow controlled release, more precise dosages and less frequent administration.

New treatment strategies

For the principal researcher of the group, Professor Alicia López Castellano, specialized in pharmaceutical technology at the CEU UCH, Dr. Alambiaga’s thesis shows that “we have demonstrated for the first time that the topical administration of progesterone in the eye is viable. strategies for patients with retinitis pigmentosa and, by extension, for patients with other eye conditions in which oxidative stress is a risk factor, such as glaucoma, age-related macular degeneration, macular edema due to retinal vein occlusion, cytomegalovirus retinitis, posterior uveitis and diabetic retinopathy.”

Parts of Dr. Adrián Alambiaga’s thesis have been published as research articles in journals such as Pharmacythe Journal of Pharmaceuticals and Biomedical Analysis, and the International Journal of Pharmacy.

Source:

Journal reference:

Alambiaga-Caravaca, AM, et al. (2022) Topical ocular administration of progesterone decreases photoreceptor cell death in mice with slow retinal degeneration (rds). Medications. doi.org/10.3390/ph15030328.

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