4.8 Article

On-demand delivery of protein drug from 3D-printed implants

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 349, Issue -, Pages 133-142

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2022.06.047

Keywords

3D printing; On-demand delivery; Remotely controlled delivery; Pulsatile multi-dose; Protein drug

Funding

  1. National Research Foundation, Ministry of Science and ICT, Republic of Korea [NRF- 2021R1A2B5B03002123, NRF-2018R1A5A2024425, 2021K2A9A2A06037695, NRF-2022M3E5F1017919]
  2. Ministry of Education, Republic of Korea [NRF-2021R1A6A3A01086428]
  3. Ministry of Health & Welfare, Republic of Korea [HI19C0664]
  4. Ministry of Health & Welfare, Republic of Korea
  5. National Research Foundation of Korea [2021K2A9A2A06037695] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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This study constructed 3D-printed multiunit implants for remote light-controlled protein drug delivery. The implants were designed to be 3D printed using a matrix of polycaprolactone, lauric acid, and melanin. Insulin was loaded into each unit of the implant, and near infrared light (NIR) was used to trigger controlled release of insulin. The results suggest that this 3D printing technology can provide convenient treatment for diabetes through external NIR irradiation, avoiding the pain and discomfort of repeated insulin injections.
Here, we constructed 3D-printed multiunit implants to enable remote light-controlled protein drug delivery in a spatiotemporal manner. Multiunit implants were designed to be 3D printed using polycaprolactone, lauric acid, and melanin as a matrix, and a polycaprolactone scaffold as a multiunit divider. As a model drug, insulin was loaded to each unit of the implant. The 3D printing yielded a rectangular matrix with multiunit sectors segre-gated by polycaprolactone lanes. Irradiation with near infrared light (NIR) triggered controlled release of insulin from the irradiated locus: Upon NIR irradiation, heat generated from the melanin melted the polycaprolactone/ lauric acid matrix to release insulin from the scaffold. In the absence of melanin in the matrix, the implant did not show NIR-responsive insulin release. When lauric acid was absent from the matrix, the NIR-irradiated unit did not undergo dismantling. When the insulin-loaded multiunit implant was applied to a mouse diabetic model and irradiated with NIR, repetitive insulin release resulted in an efficient decrease of the blood glucose level over multiple days. Together, these results suggest that 3D printing technology-based multi-dosing of insulin on de-mand can enable convenient treatment of diabetes through external NIR irradiation, potentially avoiding the pain and discomfort of repeated insulin injections.

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