Melatonin loaded hybrid nanomedicine: DoE approach, optimization and in vitro study on diabetic retinopathy model

•Reliability of Quality by Design approach in design/optimization of nanomedicine.•Stability study on optimized nanomedicine was carried out according to ICH QA(R2) guidelines resulting stable up to 6 months under refrigerated storage conditions.•Combining mucus penetrating effect and positive charges to increase mucoadhesion in ocular delivery by hybrid nanomedicine.•Neuroprotective and antioxidant effects in an in vitro model of diabetic retinopathy.•Ocular tolerability proven by a modified Draize Test.