Topical Clear Aqueous Nanomicellar Formulations for Age-Related Macular Degeneration

Abstract

Disorders affecting the posterior segment of eyes represent a significant burden to healthcare and patients’ wellbeing. Among the back of the eye disorders, age-related macular degeneration (AMD) is one of the major ailments responsible for blindness worldwide. There is currently no effective treatment available to cure AMD completely. Anti-VEGF therapy is currently considered the treatment of choice. However, it is invasive and does not offer substantial long-term relief to AMD patients. Other treatment options include thermal laser photocoagulation and surgery. None of these therapeutic approaches are safe and effective. Hence there is a real need for the development of an alternative therapeutic approach that is safe, effective and non-invasive. The objective of this study is to develop a clear, aqueous drug-loaded nanomicellar formulation utilizing FDA approved polymers, namely Hydrogenated castor oil 40 (HCO-40) and Octoxynol 40(OC-40) as a potential-therapeutics for AMD. Hydrophobic drugs such as curcumin (CUR), celecoxib (CXB), and resveratrol (RSV) were successfully solubilized and entrapped in the core of the nanomicelles. These nanomicellar constructs efficiently utilize their hydrophilic corona and evade the wash-out into the systemic circulation from both the conjunctival and choroidal blood vessels and lymphatics, thus overcoming the dynamic barrier. A design of experiments (DOE) with JMP software was performed to optimize the formulation’s size, drug loading, entrapment efficiency, critical micellar concentration (CMC), polydispersity index (PDI), zeta potential and delineate the effect of drug-polymer interactions. The formulation will be administered in the form of topical eye drops.