Anionic Surfactant-mediated Mesoporous Silica Particles for Topical Delivery of Glaucoma Drug to the Eye

Abstract

An anionic surfactant-mediated mesoporous silica (AMS), a class of amine functionalized mesoporous silica, was prepared via the S-X+I- mechanism without additional post modification processes in order to act as a carrier for brimonidine – a glaucoma drug - for the first time. Brimonidine (BRT) was used as a model drug for the topical drug delivery system to the eye to confirm the carrier effect of AMS particles. It was developed to resolve the low drug bioavailability of the glaucoma eye drop formulation caused by a very short drug residence time at the preocular surface due to the physiological eye clearance system. The amine groups at the AMS particle surface not only enhanced the encapsulation of negatively charged BRT into the AMS inner pore, but also allowed a sustained BRT release. AMS spherical particles (~1µm) with high surface area (544.1 m2/g) were successfully synthesized and fully characterized. Afterwards, BRT was encapsulated into AMS (BRT-AMS) at a reasonable drug loading amount (41.73 µg/mg). I evaluated the in vitro drug release profile of BRT-AMS where there was an initial burst of 59% for the first 20 min, followed by a sustained drug release for 8 h. The cytotoxicity test showed no toxicity to human corneal epithelial cells. To confirm the mucoadhesive property of BRT-AMS particles, in vitro and in vivo mucoadhesion studies were carried out. Approximately 0.6 mg of the 1 mg mucin was adsorbed by 2 mg of BRT-AMS particles and the zeta potential value of BRT-AMS shifted towards that of mucin. Besides, 25% of the mucoadhesive BRT-AMS particles could reside on a rabbit eye even 4 h after administration. In vivo experiments determined efficacy by assessing the change in IOP and drug bioavailability through measuring the BRT concentration in the aqueous humor (AH) of a rabbit eye. The decreasing IOP periods were 12 and 6 h after administrating BRT-AMS and Alphagan P (the commercialized medication), respectively. In addition, the BRT concentrations in AH of Alphagan P and BRT-AMS were detected for 5 and 8 h, respectively, confirming the enhanced bioavailability of BRT-AMS. Thus, it is a suitable carrier for the ocular drug delivery.