Abstract
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.
Highlights
Local instillation is the most preferred non-invasive route of administration for the treatment of eye diseases, such as glaucoma [1]
The gelation kinetics and viscoelastic properties of the ac-(RADA)4-CONH2 peptide hydrogel prior and post drug loading were evaluated with oscillatory time sweep (Figure 1A) and frequency sweep experiments (Figure 1B)
In order to further elucidate the effect of each drug compound on the rheological properties of the peptide hydrogel, the same studies were conducted on the single drug loaded peptide hydrogel (TM peptide hydrogel, brimonidine tartrate (BR) peptide hydrogel)
Summary
Local instillation is the most preferred non-invasive route of administration for the treatment of eye diseases, such as glaucoma [1]. Conventional dosage forms, such as eye drops, account for the majority Hydrogels made up of self-assembling amphiphilic peptides have gained popularity in biomedical applications, such as drug delivery systems, due to their unique properties [5]. They comprise of repetitive patterns of ionic hydrophilic and hydrophobic natural amino acids rendering them biocompatible and biodegradable. The peptide solution RADA16-I forms hydrogels of high-water content [up to 99.5% (w/w)], with a pore diameter between 5 and 200 nm, allowing entrapment and gradual release of small molecules [9,10,11,12] and macromolecules [13,14,15]
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