Fundamental investigation of sustained and controlled therapeutics release from 3D printed medical devices

Abstract

Additive manufacturing has long been acclaimed as the tool for next-generation drug delivery device production. An ongoing challenge has remained with the best method of therapeutic incorporation into these devices as the layering mechanisms associated with 3D printing can be harsh and incompatible with most drugs of interest. We propose a method of post-fabrication absorption, or post-loading, of a silicone-based matrix fabricated with digital light synthesis (DLS). The fundamental mechanisms of this process were investigated using a simplified system of blocks with varied diffusion distances. We determined the critical role of specific surface area in the swelling, uptake, and in vitro release of two model drugs, β-estradiol (hydrophobic) and 2-fluoro-2′-deoxyadenosine (hydrophilic), and found sustained drug delivery to be driven by part geometry. The drug loading method was translated to a therapeutically relevant hydrophilic antiretroviral, 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA, Islatravir®), with sustained delivery over 70 days. Finally, we demonstrated the translation of this method into a medical device (intravaginal ring) using β-estradiol as a model drug. The gentle and efficient post-loading process enables the incorporation and sustained delivery of a range of drugs and opens the door for the exploration of long-term delivery of other active pharmaceutical ingredients (APIs).