Ocular Co-Delivery of Timolol and Brimonidine from a Self-Assembling Peptide Hydrogel for the Treatment of Glaucoma: In Vitro and Ex Vivo Evaluation
Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece
Foundation for Research and Technology Hellas, Institute of Chemical Engineering and High Temperature Chemical Processes, GR-26504 Patras, Greece
Department of Materials Science, University of Patras, GR-26504 Patras, Greece
Department of Food Science and Technology, School of Agriculture, Aristotle University, GR-54124 Thessaloniki, Greece
Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece
Laboratory of Pharmaceutical Analysis, Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece
Author to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(6), 126; https://doi.org/10.3390/ph13060126
Received: 21 May 2020 / Revised: 16 June 2020 / Accepted: 20 June 2020 / Published: 21 June 2020
(This article belongs to the Special Issue Advances in Ocular Pharmacology)
Effective pharmacotherapy during glaucoma treatment depends on interventions that reduce intraocular pressure (IOP) and retain the IOP lowering effect for sufficient time so as to reduce dosing frequency and enhance patient adherence. Combination anti-glaucoma therapy and dosage forms that increase precorneal residence time could therefore constitute a promising therapeutic intervention. The in-situ gel forming self-assembling peptide ac-(RADA)4-CONH2 was evaluated as carrier for the ocular co-delivery of timolol maleate (TM) and brimonidine tartrate (BR). The hydrogel’s microstructure and mechanical properties were assessed with atomic force microscopy and rheology, respectively. Drug diffusion from the hydrogel was evaluated in vitro in simulated tear fluid and ex vivo across porcine corneas and its effect on the treated corneas was assessed through physicochemical characterization and histological analysis. Results indicated that TM and BR co-delivery affected hydrogel’s microstructure resulting in shorter nanofibers and a less rigid hydrogel matrix. Rapid and complete release of both drugs was achieved within 8 h, while a 2.8-fold and 5.4-fold higher corneal permeability was achieved for TM and BR, respectively. No significant alterations were induced in the structural integrity of the corneas treated with the hydrogel formulation, suggesting that self-assembling peptide hydrogels might serve as promising systems for combination anti-glaucoma therapy.