Self-Assembling Elastin-Like Hydrogels for Timolol Delivery: Development of an Ophthalmic Formulation Against Glaucoma

Abstract

This work focuses on improving the effectiveness of current therapies against glaucoma by incorporating self-assembled polymers into the ophthalmic formulation. To that end, we first studied the influence of the dispersing medium on the mechanical performance of self-assembling elastin-like (EL) and silk-elastin-like (SEL) hydrogels by conducting rheological tests. These polymers were subsequently incorporated into the antiglaucoma formulation, which contains timolol maleate (TM) as active ingredient, and in vivo tests, namely adhesion tests and intraocular pressure measurements (IOP), were performed in New Zealand rabbits. An enhanced reduction in IOP due to the presence of the polymers was observed. Moreover, differences in the effectiveness between both EL- and SEL-hydrogels, which can be explained on the basis of the different rheological properties displayed by these two systems, were also encountered. The results point to the potential of this system as a basis for the development of an ophthalmic formulation against glaucoma.

Self-Assembling ELR-Based Nanoparticles as Smart Drug-Delivery Systems Modulating Cellular Growth via Akt

“…12 Given their cell-friendly behaviour, tunable mechanical properties, thermal sensitivity, and ability to self-assemble, they are useful biomaterials for most applications in the fields of nanotechnology and biomedicine and, specifically, for controlled drug delivery. [13][14][15][16][17] Cancer is one of the potential applications of drug delivery systems as it is one of the most common diseases worldwide. Indeed, according to the World Health Organization, 14.1 million new cases of cancer are reported each year, with around 8.2 million cancer-related deaths.…”

Genetically Encoded Elastin‐Like Polypeptides for Drug Delivery

“…SELP hydrogels have been used as prolonged drug delivery systems for interstitial cystitis to repair the bladder mucosa, [ 69 ] as well as a treatment to reduce intraocular pressure to prevent glaucoma; [ 70 ] however, they are most commonly used in cancer therapies. [ 71 ] For example, Cappello, Ghandehari, and co‐workers have extensively studied SELPs for intratumoral, matrix‐mediated delivery of adenoviruses to improve thymidine kinase enzyme prodrug therapy in head and neck squamous cell carcinoma.…”

Advancing the stimuli response of polymer-based drug delivery systems for ocular disease treatment

“…These formulations can be instilled in the conjunctival sac of the eye without irritation or inducing tear fluid turnover, and they cause a 2-fold increase in the IOP reduction efficiency (compared to the drug solution alone), thereby maximizing the potential utility of these SRP-DDSs. 105 In addition to natural (co)polymers, synthetic copolymers such as poloxamers, PLGA-PEG-PLGA, and PEG-PLC-PEG have been intensively investigated for the development of ophthalmic SRP-DDSs. Topical instillation of a timolol maleate-loaded poloxamer allowed for the sustained release of timolol maleate, thereby improving the IOP reduction efficiency 2-fold compared to that by the administration using the drug solution alone.…”