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

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Pathologic fibrosis around silicone implants is problematic, and thus, these implants have been coated with a mixture of a biocompatible polymer and antifibrotic drug for sustained drug release to prevent fibrosis. However, a coating applied over an entire surface would be subject to mechanical instability as the implant would be severely crumpled for implant insertion. Therefore, in this work, we proposed localized, patterned coating dots, each composed of poly(lactic-co-glycolic acid) (PLGA) and tranilast, to be applied on the surface of silicone implants. The drug loaded in the pattern-coated implant herein was well retained after a cyclic tensile test. Due to the presence of PLGA in each coating dot, the tranilast could be released in a sustained manner for more than 14 days. When implanted in a subcutaneous pocket in living rats for 12 weeks, compared with the intact implant, the pattern-coated implant showed a decreased capsule thickness and collagen density, as well as less transforming growth factor-β (TGF-β) expression and fewer fibroblasts; importantly, these changes were similar between the surfaces with and without the coating dots. Therefore, we conclude that the pattern-coating strategy proposed in this study can still effectively prevent fibrosis by maintaining the physical stability of the coatings.

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