In vitro and in vivo evaluation of brimonidine loaded silica nanoparticles-laden silicone contact lenses to manage glaucoma

Abstract

Glaucoma is treated by frequent instillation of 0.2% w/v brimonidine tartrate eye drop solution, which showed poor ocular bioavailability of 1–3%. Medicated contact lenses can be used to improve the ocular drug bioavailability. However, drug loading in the contact lens matrix showed high burst release and changes the optophysical properties of the contact lens material. In this paper, a novel brimonidine loaded silica nanoparticles-laden silicone contact lenses (Bri-Si) were designed to achieve controlled drug delivery without altering the optophysical properties of the contact lens. Silica nanoparticles were prepared by polymerizing octadecyltrimethoxysilane (OTMS) molecules at the oil/water interface of microemulsion. Traditional soaking method (Bri-SM), direct brimonidine-loading method (Bri-DL) and microemulsion-laden contact lens (Bri-ME) were developed for comparison. The Bri-Si lens showed improved swelling, transmittance, oxygen permeability and lysozyme adherence compared to Bri-SM, Bri-DL and Bri-ME lenses. The Bri-DL lens showed high brimonidine leaching during extraction and sterilization steps, with low cumulative drug release. While, Bri-Si lens show controlled brimonidine release for 144 h. In a rabbit tear fluid model, the Bri-Si lens showed high brimonidine concentration for 96 h compared to Bri-ME lens and eye drop therapy. Based on histopathological studies of cornea, the Bri-Si lens was found to be safe for human applications. The data demonstrated the novel application of silica nanoparticles to control brimonidine release from the contact lens without altering the optophysical properties of the contact lens.

Innovation in the Development of Synthetic and Natural Ocular Drug Delivery Systems for Eye Diseases Treatment: Focusing on Drug-Loaded Ocular Inserts, Contacts, and Intraocular Lenses

“…Overall, regardless of the loading method that was employed, the in vitro and in vivo experiments demonstrated that silica NPs could be effective in sustaining the release of Bri. In addition, histological tests of the cornea proved that these developed drug-loaded lenses were safe and biocompatible, suggesting their possible future human use [ 92 ].…”

Application of Convergent Science and Technology toward Ocular Disease Treatment

“…Loaded lenses’ physical and optical properties were not affected, and controlled long-term release was achieved for levobunolol [ 71 ]. In a rabbit tear fluid model, silicone CLs containing brimonidine-loaded nanoparticles were prepared by Xu et al A high concentration of brimonidine was achieved for 96h with nanoparticle-loaded lenses [ 72 ].…”

Recent advancements in nanomaterial-laden contact lenses for diagnosis and treatment of glaucoma, review and update

“…The Bri-DL lens exhibited high leaching of brimonidine during extraction and sterilization, resulting in low cumulative drug release. On the other hand, the Bri-Si lens demonstrated controlled release of brimonidine for up to 144 h. In a rabbit tear fluid model, the Bri-Si lens maintained a high concentration of brimonidine for 96 h and performed better than the Bri-ME lens and eye drop therapy [ 84 ].…”