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

Abstract

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 segregated 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 demand can enable convenient treatment of diabetes through external NIR irradiation, potentially avoiding the pain and discomfort of repeated insulin injections.

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