Implantable multireservoir device with stimulus-responsive membrane for on-demand and pulsatile delivery of growth hormone

Abstract

Implantable devices for on-demand and pulsatile drug delivery have attracted considerable attention; however, many devices in clinical use are embedded with the electronic units and battery inside, hence making them large and heavy for implantation. Therefore, we propose an implantable device with multiple drug reservoirs capped with a stimulus-responsive membrane (SRM) for on-demand and pulsatile drug delivery. The SRM is made of thermosensitive POSS(MEO 2 MAco-OEGMA) and photothermal nanoparticles of reduced graphene oxide (rGO), and each of the drug reservoirs is filled with the same amount of human growth hormone (hGH). Therefore, with noninvasive near-infrared (NIR) irradiation from the outside skin, the rGO nanoparticles generate heat to rupture the SRM in the implanted device, which can open a single selected drug reservoir to release hGH. Therefore, the device herein is shown to release hGH reproducibly only at the times of NIR irradiation without drug leakage during no irradiation. When implanted in rats with growth hormone deficiency and irradiated with an NIR light from the outside skin, the device exhibits profiles of hGH and IGF1 plasma concentrations, as well as body weight change, similar to those in animals treated with conventional s.c. hGH injections. drug delivery | implantable device | near-infrared light | stimulusresponsive membrane

Electrostatically gated nanofluidic membrane for ultra-low power controlled drug delivery

“…69 In these applications, our technology could emulate the function of the body by providing hormone release profiles that mimic the circadian cycle of hormone secretion. 70 In vitro release modulation of DNA salt…”

“…Alternatively, magnetic particles, can be controlled by an external magnetic field and can act as valves to open or close the membrane. 19,20 These technologies are valuable strategies for controllable drug delivery. However, they require continuous external intervention to function, which compromises their application to the next generation of autonomous drug delivery systems.…”

Silicon Nanofluidic Membrane for Electrostatic Control of Drugs and Analytes Elution

“…These systems mostly rely on polymeric membrane architectures and achieve changes in pore size and conformation via temperature variation triggered by a magnetic field [ 21 ], near-infrared irradiation [ 22 , 23 , 24 ], or ultrasound [ 25 ]. Other devices use a magnetic field to reversibly or irreversibly obstruct the pores of a membrane using microparticles [ 26 ] or low melting temperature polymers [ 27 ]. Albeit promising, these strategies are limited by the need for continuous external activation and associated cumbersome external equipment.…”

Recent Advances in Micro-Electro-Mechanical Devices for Controlled Drug Release Applications

“…The use of actuation mechanisms based on non-invasive infrared radiation began to be investigated very recently. In this sense, stimulus responsive membranes were used for capping drug reservoirs in an implantable device ( Lee et al, 2019 ). These membranes were made of thermosensitive polymer hybrid [POSS (MEO2MAco- OEGMA)] and photothermal nanoparticles of reduced graphene oxide.…”

“…(C) Optical images of the device and external guide (scale bar: 1 cm). Reproduced from Lee et al (2019) with permission from the National Academy of Sciences of the United States of America.…”