Development of a nanogel based topical drug formulation for the treatment of neovascular age-related macular degeneration (nAMD)

Official URL: https://risc01.sabanciuniv.edu/record=b2767126_(Table of contents)

Age-related macular degeneration (AMD) is a complex eye disease leading irreversible vision loss of mostly 65 years-old or older individuals. AMD accounts for 8.7 % of blindness globally and an estimate of one of five people in aging populations (60-year-old or more), one of five people may have this disease. AMD is classified into two main types: early AMD and late AMD. Late AMD may be distinguished in two forms: wet (neovascular) and dry (non-neovascular) AMD. Early stages AMD is characterized by changes occurred in retinal pigment epithelium (RPE) and drusen (small yellowish white deposits) formations. Laser photocoagulation and injection of VEGF inhibitors (ranibizumab, bevacizumab, aflibercept, and pegaptanib, brolucizumab, abicipar, conbercept, faricimab, pazaopanib) are the approaches for AMD treatment. However, there are several patients, who do not respond well to these treatments or face with side effects such as pain and infection. In addition, the treatment is costly and experienced professionals are required to perform intravitreal injections. The aim of this study is to develop a topical nanodrug formulation with less cost of production, capable of crossing the anatomical and physiological barriers of the eye. To this aim, an anti-VEGF peptide that has high affinity to VEGF-Fc receptor was used as the bioactive agent to control neovascularization of retina. In this nano formulation, a cell penetrating peptide (penetratin peptide) and hyaluronic acid (HA), which is specific to retina were combined with the anti-VEGF peptide. To increase the stability and control the size of the nanodrug, divinyl sulfone (DVS) and cholesterol were used, respectively. Initial results on HUVE cells and ARPE-19 cells indicate that nanodrug inhibits HUVE cell proliferation in a dose dependent manner, whereas it does not affect ARPE-19 cells proliferation. Encapsulation efficacy of nanogels 4 were 65 % and 53 % for nanogel 1 and nanogel 2, respectively. Drug release was 34,72 % from nanogel 1 at the end of 192 hours, and 36% of drug was released from nanogel 2 at the end of 24 hours. We believe that nanogels formulated in this study can be improved and investigated further as a potential AMD treatment approach. The promising data obtained from in vitro studies should also be validated with in vivo models to confirm the efficiency of the nanodrugs.