We have developed polyurethane nanocapsules as a platform for long-term delivery of drugs over weeks as well as on-demand delivery of drugs via ultrasound. We synthesized nanocapsules encapsulating either a model drug, fluorescein, or a clinically relevant drug, acriflavine, a HIF-1alpha inhibitor. Release studies demonstrated delivery of fluorescein or acriflavine over several weeks. Application of either an ultrasonic probe or a clinical grade, ultrasound imaging system used for assessing the retina led to release of a fraction of drug that could be tailored by the energy applied to the nanocapsules, and multiple pulses of release could be triggered over time with at least 10 separate release events triggered for each formulation. Being able to tailor the on-demand release over multiple cycles has the potential to fundamentally change how we can approach delivery of drugs for a variety of applications.