(65a) Triggerable Tissue Depth of Externally-Triggerable Drug Delivery Systems for on-Demand Nerve Block

Externally triggerable drug delivery systems have provided promise in personalized drug delivery where the time and site of drug release can be controlled by the caregiver or patient, non-invasively and effectively. However, major limitations stand in the path of translation of these systems, one of which is the applicability of activating such drug delivery systems in deep tissues, at the target site. Here, developed ex vivo and validated in vivo, we studied the tissue depth-dependence of externally-activated drug release from drug delivery systems. We developed an approach predict the payload release at varying tissue depths, and the results were validated by experimental results ex vivo and in vivo nerve block models. Light and ultrasound were chosen as the external triggers as many drug delivery systems have been developed based on these energy sources and they possess desirable properties as external triggers: ultrasound has been considered to penetrate tissue effectively, and near infrared light penetrates deeper than UV or visible light. We found that the key factor to achieve payload release at the desired tissue depth was not only the tissue penetrating properties of the energy source, but also the sensitivity of the drug delivery system towards the external energy.

Our results demonstrated that two important parameters should be considered for the activation of drug delivery systems in deep tissue: 1) the ability of the activation energy to penetrate tissue, 2) the sensitivity of the system to the activation source. Although ultrasound penetrated through tissue more effectivly than near-infrared light, the higher sensensitivity of the light-triggerable system allowed more effective cargo release at tissue depths between 0 and 2 cm. In vivo nerve block results demonstrated that our theoretical model provided a reasonable estimate of the activated release at different tissue depths.