Emergency delivery of particulate drugs by active ejection using in vivo wireless devices.

Abstract

Rapidly administered emergency drug therapy represents life-saving treatment for a range of acute conditions including hypoglycaemia, anaphylaxis and cardiac arrest. Devices that automate emergency delivery, such as pumps and automated injectors, are limited by the low stability of liquid formulations. In contrast, dry particulate formulations of these drugs are stable but are incompatible with drug pumps and require reconstitution before administration. Here we develop a miniaturized (<3 cm³), lightweight (<2 g), minimally invasive, fully wireless emergency rescue device for the storage and active burst-release of indefinitely stable particulate forms of peptide and hormone drugs into subcutaneous sites for direct reconstitution in interstitial biofluids and rapid (<5 min) therapeutic effect. Importantly, the device delivers drug across fibrotic tissue, which commonly accumulates following in vivo implantation, thereby accelerating systemic delivery. Fully wireless delivery of dry particulate glucagon in vivo is demonstrated, providing emergency hypoglycaemic rescue in diabetic mice. In addition, triggered delivery of epinephrine is demonstrated in vivo. This work provides a platform for the long-term in vivo closed-loop delivery of emergency rescue drugs.