In Vivo rapid delivery of vasopressin from an implantable drug delivery micro-electro-mechanical device

Hong Linh Ho Duc, Noel Elman, Alison M. Hayward, Dustin J. Rabideau, Michael J. Cima

Abstract


A miniaturized implantable rapid drug delivery device based on micro-electro-mechanical-systems technology was recently developed and characterized. This device is intended to address acute conditions in high-risk subjects. This work provides an in vivo proof-of-concept for the device in a rabbit model, by releasing a physiologically active dose of vasopressin, a vasoconstrictor. The devices were implanted subcutaneously and activated to rapidly release vasopressin, with monitoring of mean arterial pressure and plasma levels.Device releases showed a rapid and measurable effect on mean arterial pressure as well as a continuous diffusion of vasopressin into the bloodstream, consistent with a depot effect. Plasma levels in rabbits receiving vasopressin with the device rose monotonically to 24.4 ± 2.9 ng/mL after one hour. Bioavailability after one hour was calculated to be 6.2 ± 2.8 % (mean ± s.d.).A new modality for rapid and controlled drug delivery has been developed. The device can be used as a new implantable device controlled by medical algorithms (based on heart rate or mean arterial pressure, for example) for autonomous operation in high-risk populations that require immediate ambulatory intervention.

Keywords: Subcutaneous drug delivery; vasopressin; MEMS; rabbit; bioavailability.


Keywords


Subcutaneous drug delivery; vasopressin; MEMS; rabbit; bioavailability.

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