Novel nanocarriers to improve drug delivery for age-related macular degeneration
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Visual impairment affecting the posterior segment of the eye is a significant health problem causing a deterioration of the quality of life of millions worldwide. Age-related macular degeneration (AMD) is ranked third on a global scale as one of the major back-of-the-eye disorders being responsible for blindness in elderly patients over 60 years. As there is no efficacious cure to completely prevent AMD, the invasive anti-VEGF therapy is currently a treatment of choice which does not provide long-term comfort to AMD patients. Other treatment options such as surgery and thermal laser photocoagulation did not appear to be safe for long-term treatment. Hence it is crucial to develop an effective, safe and non-invasive treatment method. The hypothesis of this study was to develop aqueous, clear and drug-loaded nanomicellar formulations using FDA-approved polymers namely Hydrogenated castor oil 40 (HCO-40), Octoxynol-40 (OC-40) and Vitamin E TPGS as potential delivery cargos to treat AMD. Lipophilic drugs such as etodolac (ETD), oxaprozin (OXP) and indomethacin (IN) were successfully encapsulated in the hydrophobic core of the nanomicelles with enhanced solubility. Nanomicellar formulations decorated with hyaluronic acid (HA) were utilized as the cellular uptake enhancer in oxaprozin-loaded nanomicelles into retinal cells. These formulations are capable to overcome the ocular static and dynamic barrier caused by the systemic circulation from the conjunctival and choroidal blood vessels because of their very low critical micellar concentration and nanomicellar size. To optimize and depict the effect of drug-polymer interactions, a design of experiments (DOE) with JMP software was performed to determine the formulations’ size, critical micellar concentration (CMC), entrapment and loading efficiency, zeta potential, optical clarity and morphology. The optimized formulations are promising for topical application.
Table of Contents
Introduction -- Ocular anatomy and drug delivery -- Self-assembled etodolac loaded topical nanomicellar formulation for retinal drug delivery -- Self-assembled hyaluronic acid decorated nanomicellar formulation of oxaprozin for back of the diseases -- Indomethacin-loaded vitamin E TPGS polymeric-nanomicelles as a potential treatment for retinal diseases -- Summary and recommendations -- Appendix A. Abbreviations -- Appendix B. Permissions
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Ph.D. (Doctor of Philosophy)