Design of Antioxidant Encapsulated Polymeric Micro- or Nano-drug Delivery Systems for Ischemic Stroke Treatment

Ischemic stroke is a leading cause of adult death and disability worldwide. However, current ischemic stroke drug treatments remain inadequate. Due to the severity of the ischemic stroke, there is an urgent need to develop effective drug delivery systems with better temporal and spatial controls of drug releases. We propose delivering antioxidant drugs, with temporal and spatial controls, via polymeric microcarriers for directly injection to the stroke lesion and via polymeric nanocarriers for an easier and less invasive intravenously injection. The delivered antioxidants that released from the polymeric micro/nanoparticles will scavenge reactive oxygen species (ROS) generated after ischemic stroke. In the thesis, we discuss the loadings and release profiles of antioxidants encapsulated polymeric microparticles (MPs) (single-wall and core-shell (in theory, the shell phase could act as a diffusive barrier to avoid the burst release of the drug encapsulated in the core phase and to support the sustained release) MPs) and dynamic light scattering (DLS) sizes of single-wall MPs sizes. We also focus on the antioxidant encapsulated polymeric nanoparticles (NPs) in this thesis. NPs were fabricated via nanoprecipitation and the sizes were measured by DLS. We control nanoparticle size via polymer concentration and molecular weight with our smallest untargeted antioxidant nanoparticles having a 106.52+/- 0.40 nm diameter. This size provides the potential for surface modification while maintaining a ~200nm target size limit. The reconstituted NPs with preserved sizes after freeze-drying steps could be achieved by adding appropriate concentration of sucrose, a cryo/lyoprotectant, before lyophilizations.