Silica-based composite nanoparticles as pH-responsive drug carriers and their application in contact lens drug delivery
Type of DegreePhD Dissertation
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Controlled drug delivery from contact lenses is an attractive method to treat ocular disease, like glaucoma, as it overcomes the deficiencies of traditional eye drops, such as poor patient adherence and low bioavailability. With controlled delivery from contact lenses, drug molecules have a longer residence time in the post-lens tear film, which ultimately leads to a higher drug flux through the cornea and a lowered possibility of toxic side effects. The goal of this project is to design a novel contact lens device with integrated pH-responsive nanocomposite particles that trigger drug release under physiological pH conditions. Biocompatible drug carriers, with the ability to control delivery of therapeutic agents, are a promising way to overcome the limitations of conventional therapies. Among all types of carriers, silica-based nanocomposites have emerged as a promising candidate because of its biocompatibility and high physical and chemical stability. Moreover, silica-based, pH-responsive nanocomposite materials can be produced by encapsulation of natural or synthetic pH-responsive polymers, such as alginate, chitosan, poly (methacrylic acid) and poly (acrylic acid). In this work, silica-alginate composite materials were prepared with different structures, such as alginate beads loaded with silica nanoparticles, silica-alginate monolithic gels, and silica-alginate nanoparticles. All of them showed a pH-responsive release of rhodamine B, which was used as a model drug. In this dissertation, the focus was on pH-responsive silica-based composite nanoparticles synthesizes using silica sol-gel chemistry and formed in a water-in-oil microemulsion system. Different polymer (alginate, poly(methacrylic acid)) solutions were used as the water phase for the formation of silica-polymer nanoparticles. Nano-sized particles between 20-80 nm were detected by transmission electron microscopy. Silica-alginate composite nanoparticles showed no significant pH-responsive release of timolol maleate, which is a commonly used drug for glaucoma treatment. However, silica-PMAA nanoparticles displayed encouraging pH-responsive release of timolol maleate with only a fraction of drug released at low pH and then continuous, sustained release at physiological pH. These particles demonstrated the concept of ON/OFF triggered release with < 15% drug released under pH 2.5 and a long, sustained release of drug in simulated tear fluid. The inclusion of nanoparticles did not adversely affect important properties of contact lens like optical clarity and water content. Encouraging pH-responsive release profiles were also observed for silica-PMAA nanoparticles incorporated contact lenses. Those lenses showed limited release of timolol maleate in low pH buffer solution and much higher release of timolol maleate in simulated tear fluid. This promising pH-responsive release performance of silica-PMAA nanoparticles incorporated contact lens shows the potential of a good candidate for commercial contact lens drug delivery vehicles.