Abstract
On-demand, localized release of drugs in precisely controlled, patient-specific time sequences represents an ideal scenario for pharmacological treatment of various forms of hormone imbalances, malignant cancers, osteoporosis, diabetic conditions and others. We present a wirelessly operated, implantable drug delivery system that offers such capabilities in a form that undergoes complete bioresorption after an engineered functional period, thereby obviating the need for surgical extraction. The device architecture combines thermally actuated lipid membranes embedded with multiple types of drugs, configured in spatial arrays and co-located with individually addressable, wireless elements for Joule heating. The result provides the ability for externally triggered, precision dosage of drugs with high levels of control and negligible unwanted leakage, all without the need for surgical removal. In vitro and in vivo investigations reveal all of the underlying operational and materials aspects, as well as the basic efficacy and biocompatibility of these systems.
Highlights
Macroscale drug delivery devices offer advantages over systemic particulate approaches with respect to target efficiency, nuclease degradation and renal clearance.[1]
A key disadvantage is that surgical procedures must be used to extract the implanted hardware after completion of the delivery function. Alternative strategies include those that use lipid-based materials as hosts for drugs such as doxorubicin, where ex situ hyperthermic treatments based on radio frequency ablation,[9] microwaves[10] or focused ultrasound,[11] can trigger thermally activated release
This paper reports an important advance that follows from the combined use of temperature-sensitive lipid-based layered films with electronically programmable, frequency-multiplexed wireless hardware
Summary
Macroscale drug delivery devices offer advantages over systemic particulate approaches with respect to target efficiency, nuclease degradation and renal clearance.[1]. Adjustable and patient-specific operation can be achieved with electronically programmable systems that exploit remotely triggered opening of valves built into combined fluidic and electronic platforms.[6,7,8] A key disadvantage is that surgical procedures must be used to extract the implanted hardware after completion of the delivery function. Alternative strategies include those that use lipid-based materials as hosts for drugs such as doxorubicin, where ex situ hyperthermic treatments based on radio frequency ablation,[9] microwaves[10] or focused ultrasound,[11] can trigger thermally activated release. Our recent work[14] demonstrated bioresorbable systems for in situ operation, but with only single-channel control over a single type of drug from a single reservoir, where matrices of silk fibroin allowed adjustment of release rates across a narrow range above a fixed, intrinsic baseline value
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