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

Seung Ho Lee, Huiyan Piao, Yong Chan Cho, Se Na Kim, Goeun Choi, Cho Rim Kim, Han Bi Ji, Chun Gwon Park, Cheol Lee, Chong In Shin, Won Gun Koh, Young Bin Choy, Jin Ho Choy

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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(MEO2MA-co-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.

Original languageEnglish
Pages (from-to)11664-11672
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number24
DOIs
Publication statusPublished - 2019 Jun 11

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Lee, S. H., Piao, H., Cho, Y. C., Kim, S. N., Choi, G., Kim, C. R., Ji, H. B., Park, C. G., Lee, C., Shin, C. I., Koh, W. G., Choy, Y. B., & Choy, J. H. (2019). Implantable multireservoir device with stimulus-responsive membrane for on-demand and pulsatile delivery of growth hormone. Proceedings of the National Academy of Sciences of the United States of America, 116(24), 11664-11672. https://doi.org/10.1073/pnas.1906931116