Externally Addressable Smart Drug Delivery Vehicles: Current Technologies and Future Directions

Growing clinical evidence around the value of delivering drugs with pulsatile, user-controlled, or patient-specific kinetics has recently resulted in extensive efforts toward the design of new functional materials that can enable on-demand externally triggered drug release using noninvasive or minimally invasive stimuli such as temperature changes, magnetic fields, light, ultrasound, and/or electric fields. While substantial technical improvements have been made toward achieving longer-term and user-defined release kinetics from such materials (based principally on innovation in materials design and the development of various triggering modalities), clinical translation of such technologies remains in its infancy; specifically, multiple residual challenges exist around the chemical complexity, biological responses, and predictability of externally triggered release vehicles when used in vivo. In this perspective, we aim to outline major recent advances in the development of externally triggered drug delivery vehicles with improved performance both in vitro and in vivo and describe ongoing and emerging research challenges that, if overcome, can accelerate the translation of such technologies from the bench to the bedside.