Implantable system for chronotherapy

SH Lee, Q Wan, A Wentworth, I Ballinger, K Ishida… - Science …, 2021 - science.org
Science Advances, 2021science.org
Diurnal variation in enzymes, hormones, and other biological mediators has long been
recognized in mammalian physiology. Developments in pharmacobiology over the past few
decades have shown that timing drug delivery can enhance drug efficacy. Here, we report
the development of a battery-free, refillable, subcutaneous, and trocar-compatible
implantable system that facilitates chronotherapy by enabling tight control over the timing of
drug administration in response to external mechanical actuation. The external wearable …
Diurnal variation in enzymes, hormones, and other biological mediators has long been recognized in mammalian physiology. Developments in pharmacobiology over the past few decades have shown that timing drug delivery can enhance drug efficacy. Here, we report the development of a battery-free, refillable, subcutaneous, and trocar-compatible implantable system that facilitates chronotherapy by enabling tight control over the timing of drug administration in response to external mechanical actuation. The external wearable system is coupled to a mobile app to facilitate control over dosing time. Using this system, we show the efficacy of bromocriptine on glycemic control in a diabetic rat model. We also demonstrate that antihypertensives can be delivered through this device, which could have clinical applications given the recognized diurnal variation of hypertension-related complications. We anticipate that implants capable of chronotherapy will have a substantial impact on our capacity to enhance treatment effectiveness for a broad range of chronic conditions.
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