Picoliter‐volume inkjet printing into planar microdevice reservoirs for low‐waste, high‐capacity drug loading

Abstract

Oral delivery of therapeutics is the preferred route for systemic drug administration due to ease of access and improved patient compliance. However, many therapeutics suffer from low oral bioavailability due to low pH and enzymatic conditions, poor cellular permeability, and low residence time. Microfabrication techniques have been used to create planar, asymmetric microdevices for oral drug delivery to address these limitations. The geometry of these microdevices facilitates prolonged drug exposure with unidirectional release of drug toward gastrointestinal epithelium. While these devices have significantly enhanced drug permeability in vitro and in vivo, loading drug into the micron‐scale reservoirs of the devices in a low‐waste, high‐capacity manner remains challenging. Here, we use picoliter‐volume inkjet printing to load topotecan and insulin into planar microdevices efficiently. Following a simple surface functionalization step, drug solution can be spotted into the microdevice reservoir. We show that relatively high capacities of both topotecan and insulin can be loaded into microdevices in a rapid, automated process with little to no drug waste.

Microfabricated devices for oral drug delivery

“…In initial attempts to load Si micropatches, microinjection has been used to inject biopolymer compounds dissolved in an aqueous solution into microcontainers 31,43 . After this, inkjet printing of solutions has been evaluated on several occasions ( Figure 3A) 31,43,44 . Despite these attempts, the printing technique has not been established as the preferred method for direct loading of drug.…”

“…To be competitive, the advantages obtained using microfabricated devices have to be considerable, and thorough in vitro and in vivo evaluation is important. In vitro studies are preferably carried out before any in vivo studies as they C) Photolithography 6,10,17 D) Manual powder filling 11,25 A) Inkjet printing 31,43,44 B) CO 2 impregnation [45][46][47] E) Powder embossing 48 F) Spin coating and hot punching 49 often give a good indication on how the microdevices and the API will perform. To realize a good correlation between in vitro and in vivo studies, the in vitro studies should be as close to the in vivo situation as possible.…”

Editorial: The launch phase of Bioengineering & Translational Medicine

“…In terms of scientific topics, BioTM has focused on subjects where Engineering, Chemical Engineering in particular, has made a strong fundamental and translational impact on the field. These topics include drug delivery, Nucleic acid delivery, Regenerative Medicine, Biotechnology, Nanomedicine, Biomedical Devices, and immunotherapy . We look forward to continue building our strengths in these fields and expand the list to include additional key areas.…”

Introduction to special issue: Bioengineered Therapeutics. The Next Generation of Drug Development

“…There is a conscious paradigm shift to combine discovery and delivery efforts early in the drug development process to mitigate failure. Seven contributions in this issue discuss novel approaches, both synthetic and biomimetic, to achieve effective delivery by employing discoveries and innovations in biology, immunology, biochemistry, biophysics, and micro‐fabrication . Champion and colleagues describe the biochemical tailoring of nanoparticles with molecular adjuvants to generate specific effector responses against pathogens that offer superior vaccination against infectious diseases .…”

“…Swartz and colleagues review the potential for use of virus like particles (VLPs) as highly effective delivery vehicles that overcome the many challenges encountered in targeted delivery of therapeutic cargoes . Desai and colleagues demonstrate inkjet printing of therapeutics in microdevices to circumvent the challenges of low bioavailability, degradation, poor cellular permeability, and low residence time for oral administration . Goto and colleagues describe a simple and easy to use vaccine administration method using a solid‐in‐oil nanodispersion system incorporating immunomodulatory adjuvants for soliciting specific immune responses via transcutaneous vaccination .…”