Since biological systems exhibit a circadian rhythm (24-hour cycle), they are susceptible to the timing of drug administration. Indeed, several disorders require a therapy that synchronizes with the onset of symptoms. A targeted therapy with spatially and temporally precise controlled drug release can guarantee a considerable gain in terms of efficacy and safety of the treatment compared to traditional pharmacological methods, especially for chronotherapeutic disorders. This paper presents a proof of concept of an innovative pulsatile drug delivery system remotely triggered by the acoustic radiation force of ultrasound. The device consists of a case, in which a drug-loaded gel can be embedded, and a sliding top that can be moved on demand by the application of an acoustic stimulus, thus enabling drug release. Results demonstrate for the first time that ultrasound acoustic radiation force (up to 0.1 N) can be used for an efficient pulsatile drug delivery (up to 20 µg of drug released for each shot).

Goal: We analyze temperature dynamics in anatomic pathology samples to identify the most efficient refrigeration method and to predict the time available for an optimal sectioning before sample heating, thus to get appropriate information for a correct diagnosis by anatomopathologists. Methods: A thermal Finite Element (FE) analysis was carried out with COMSOL Multiphysics to evaluate temperature variations in paraffin-embedded tissues, i.e., muscle, bone and fat. Experiments with different tissues and thermocouple-based measurements allowed to validate the FE simulations. Results: Simulations allowed to estimate the time needed to bring the sample at the optimal temperature for sectioning (-8 - -4 °C) in different conditions: refrigeration on a cold plate, refrigeration in a cooled environment and refrigeration in an environment with a forced convection. Among the three cooling methods tested the last one resulted the most efficient. A cooling temperature of -20 °C was the most effective, among the ones tested. For the different conditions, the time needed for the surface of the tissue block to exit from a temperature corresponding to an optimal cutting, when leaving the sample expose to room temperature after refrigeration, ranged from 12s to 310 s. Conclusions: We quantify the time needed to adequately refrigerate paraffin-embedded tissue samples and the time available before they leave the optimal temperature window for sectioning. This information will be helpful in optimizing anatomic pathology processes.