The present invention relates to methods to guide the engineering of nanoparticle drugs for intravenous administration based on various pharmacokinetic parameters and other tests. The methods of the present invention have particular use in formulating nanoparticles containing cytotoxic drugs for the treatment of cancer. The guiding principles are properties which facilitate the release of drugs into the patient including unstable in plasma/blood, low AUC, low Cmax, high Vd, CMC above experimental Cmax of the drug, high tumor/plasma AUC. The present invention also provides for methods of administration and compositions which are unstable after administration to a patient so that the cytotoxic drug may bind to endogenous drug transporters and be delivered to tumors in the patient.
