Cancer is a deadly disease that affects many people in the world. Even though there have been major technological advancements in the field that improve early cancer detection capabilities and provide new drugs, cancer patient survival has not improved significantly. One reason for this is current drug testing approaches do not reliably and accurately assess the effectiveness of the drug. Nanoparticle delivery of chemotherapeutic drugs shows a lot of promise for improving cancer treatment because they can decrease systemic toxicity; however, the tests for their efficacy do not mimic the actual physiological environment. Here, we create lipid hybrid polymer nanoformulations of doxorubixin and evaluate the efficacy in three dimensional tumor spheroids in comparison to the standard testing in two dimensional wells. The nanoparticles are synthesized by either microfluidics or multivortex mixers. They are characterized by Transmission Electron Microscopy (TEM), Atomic force Microscopy (AFM), Drug elution. The controlled release of the doxorubicin is evaluated and cytotoxicity in spheroids and 6 well plates are compared and contrasted. The results reveal how nanoparticle formulations can be made repeatedly and evaluated more accurately than they are with standard cytotoxicity tests.