New antiglaucomatous agent for the treatment of open angle glaucoma: Polymeric inserts for drug release and in vitro and in vivo study

Abstract

A benzamidine derivative from diminazene was tested for a novel activity: treatment of primary open‐angle glaucoma. This drug was incorporated into mucoadhesive polymeric inserts prepared using chitosan (Chs) and chondroitin sulfate (CS). Of current interest is the mucoadhesion, which increases the contact time with the ocular surface, resulting in improved bioavailability; also, the inserts are made to act as a prolonged release system. In the present work the inserts were prepared by the solvent casting method using different polymeric proportions (30:70, 50:50, 75:25% w/w Chs:CS and 100% Chs). Thermal analysis and infrared spectroscopy both demonstrated physical dispersion of the active drug. The most promising was the 50:50% Chs:CS which demonstrated that it was not fragile and has an in vitro release profile of up to 180 minutes. In addition, it presented greater adhesion strength in relation to the other formulations. These physicochemical results corroborate the in vivo tests performed. In this sense, we also demonstrated that the treatment with the 50:50% insert can control the intraocular pressure (IOP) for at least 3 weeks and prevents damage to the retinal ganglion cells (RGCs) compared to the placebo insert. Thus, this indicates thus that the new drug is quite viable and promising in glaucoma treatment.

Novel Biomaterials in Glaucoma Treatment

“…Mucoadhesive polymeric inserts prepared using CH and chondroitin sulfate were used as DDSs for benzamidine in the research of Cesar et al This study showed promising results for anti-glaucoma treatment [57].…”

Breaking Barriers in Eye Treatment: Polymeric Nano-Based Drug-Delivery System for Anterior Segment Diseases and Glaucoma

“…Several studies have used chitosan, a highly biodegradable polymer, to develop ocular inserts and films for topical delivery. Modifications were carried out to improve the solubility of chitosan, such as the addition of chondroitin sulfate and hydroxyethyl cellulose [ 65 , 66 ]; these modified chitosan inserts were able to lower IOP by delivering 4-aminodiphenylamine (a benzamidine derivative) and dorzolamide, respectively. Interestingly, with a sustained release, both drugs also exhibited a neuroprotective effect towards the retinal ganglion cells (RGC).…”

Neuartige Wirkstoffabgabesysteme für die Glaukomtherapie: Hürden und Lösungsansätze für die Formulierung

“…Okuläre Inserte nur mit CS werden für verschiedene Wirkstoffe zur Glaukombehandlung entwickelt, z.B. für Bimatoprost [212], Brimonidintartarat [213] und Diminazen [214], außerdem in Kombination mit Hydroxyethylcellulose für Dorzolamid [215] und in Kombination zu gleichen Teilen mit Chondroitinsulfat für Diminazen [216].…”