Drug delivery-enhancing platforms are vital to overcoming the blood-brain barrier that prevents sufficient accumulation of drugs in the brain during treatment. Although nanoparticles can improve the treatment of neurological diseases, such as Alzheimer’s disease, the formulation process must be optimized because an inadequate amount of drug can currently be loaded in nanoparticles. The goal of my project is to 1) optimize nanoparticle formulation parameters to maximize therapeutic enzyme activity, and 2) characterize the extent of nanoparticle degradation due to sonication. Within part 1), formulation methods were composed of poly(lactic-co-glycolic) acid copolymerized with poly(ethylene glycol), cholic acid (CHA) or polyvinyl alcohol surfactant, and the enzyme catalase. I formulated each of the nanoparticles at varied sonication times during the emulsion step to measure differences in therapeutic activity using UV-Vis spectroscopy. I found that the 30s sonicated CHA double emulsion and nanoprecipitation methods yielded the greatest enzymatic activity, 2.10% and 3.72% activity, respectively. In the presence of degradative pronase, CHA double emulsion nanoparticles exhibited better retention of enzymatic activity than nanoprecipitation, 75.66% and 9.22% retention, respectively. Within part 2), I monitored heat flow to identify the melting temperature in a sample of PEG exposed to varying sonications and assessed PEG degradation using differential scanning calorimetry. 5kDa PEG exhibited a melting temperature of 60.792C, while 5kDa PEG exposed to 2x150s of sonication exhibited a melting temperature of 59.450C, correlating to 4.8kDa. The 30s sonication CHA double emulsion formulation yielded the highest enzymatic activity with protection from degradation from external proteases. Thus, my results point to a promising polymeric nanoparticle design that may help in the development of more powerful and effective treatment options for neurological diseases.