|dc.description.abstract||Dry eye disease is a highly prevalent condition that affects hundreds of millions of people worldwide. In moderate to severe cases, affected individuals experience considerable difficulty in carrying out their day-to-day activities due to discomfort and pain, and may even develop symptoms of depression. Ocular lubricants (sometimes referred to as artificial tears) are the most widely-used method of dry eye management. Despite being available over-the-counter and in myriad varieties and brands, current formulations all suffer from either short duration of action or high inconvenience due to vision obstruction, unwanted residue, and/or invasiveness. There is therefore great need for long-lasting, inconspicuous, and convenient ocular lubricant formulations to address the shortcomings of current market offerings.
This thesis describes the development of a novel ocular lubricant technology based on mucoadhesive dextran hydrogel nanoparticles (DH-NPs) that shows considerable promise in addressing these needs. The nanoparticles feature a dextran hydrogel core and are capable of sustained release of ocular lubricant. The nanoparticles are also modified to impart mucoadhesion and are thereby expected to be retained on the ocular surface for approximately 24 hours. By continuously releasing lubricant during this time, DH-NPs are anticipated to provide long-lasting and more effective DED symptom relief than the ocular lubricants currently on the market.
In addition to the methods of DH-NP synthesis and characterization, various parameters capable of tuning key properties such as diameter, synthesis yield, PBA conjugation, and mucoadhesion strength are described herein. In vitro release experiments were also performed to characterize the kinetics of ocular lubricant release from DH-NPs. Various parameters that affect release rate and quantity were identified to enable tuning and optimization towards achieving the ideal clinical ocular lubricant dose. An acute in vivo biocompatibility study was also performed using a rabbit model, in which the novel formulation was well-tolerated. Overall, DH-NPs were found to be a highly promising technology for DED treatment, and further development towards clinical evaluation is recommended.||en