Abstract
The increment in ocular drug bioavailability after topical administration is one of the main challenges in pharmaceutical technology. For several years, different strategies based on nanotechnology, hydrogels or implants have been evaluated. Nowadays, the tolerance of ophthalmic preparations has become a critical issue and it is essential to the use of well tolerated excipients. In the present work, we have explored the potential of gelatin nanoparticles (GNPs) loaded with timolol maleate (TM), a beta-adrenergic blocker widely used in the clinic for glaucoma treatment and a hybrid system of TM-GNPs included in a hydroxypropyl methylcellulose (HPMC) viscous solution. The TM- loaded nanoparticles (mean particle size of 193 ± 20 nm and drug loading of 0.291 ± 0.019 mg TM/mg GNPs) were well tolerated both in vitro (human corneal cells) and in vivo. The in vivo efficacy studies performed in normotensive rabbits demonstrated that these gelatin nanoparticles were able to achieve the same hypotensive effect as a marketed formulation (0.5% TM) containing a 5-fold lower concentration of the drug. When comparing commercial and TM-GNPs formulations with the same TM dose, nanoparticles generated an increased efficacy with a significant (p < 0.05) reduction of intraocular pressure (IOP) (from 21% to 30%) and an augmentation of 1.7-fold in the area under the curve (AUC)(0–12h). On the other hand, the combination of timolol-loaded nanoparticles (TM 0.1%) and the viscous polymer HPMC 0.3%, statistically improved the IOP reduction up to 30% (4.65 mmHg) accompanied by a faster time of maximum effect (tmax = 1 h). Furthermore, the hypotensive effect was extended for four additional hours, reaching a pharmacological activity that lasted 12 h after a single instillation of this combination, and leading to an AUC(0–12h) 2.5-fold higher than the one observed for the marketed formulation. According to the data presented in this work, the use of hybrid systems that combine well tolerated gelatin nanoparticles and a viscous agent could be a promising alternative in the management of high intraocular pressure in glaucoma.
Highlights
Glaucoma is considered as a group of ocular chronic disorders characterized by a distinctive neuropathy that leads to a progressive asymptomatic visual field loss
The aim of the present work is to evaluate the combination of two technological strategies to increase the ocular bioavailability of timolol maleate (TM), an ocular hypotensive drug widely used in the clinic for glaucoma treatment
We have explored the potential of a hybrid system composed by gelatin nanoparticles loaded with TM, included in a hydroxypropyl methylcellulose viscous solution
Summary
Glaucoma is considered as a group of ocular chronic disorders characterized by a distinctive neuropathy that leads to a progressive asymptomatic visual field loss. The maintained increase of IOP is triggered by the accumulation of aqueous humour in the anterior chamber of the eye due to a distortion between its production and its outflow through the trabecular meshwork This high pressure is transmitted to the posterior segment of the eye and to the retina and optic nerve head promoting the progressive death of the retinal ganglion cells (RGCs) and inducing the loss of vision [3]. Among the main therapeutic agents, non-selective β- antagonists such as timolol maleate (TM), betaxolol or carteolol are widely employed as first-line therapy because of their efficacy at reducing IOP [4]. These drugs reduce aqueous humour by inhibition of AMPc synthesis via antagonization of the β-adrenergic receptors present in the ciliary body cells [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
