3D-Printed Radiopaque Microdevices with Enhanced Mucoadhesive Geometry for Oral Drug Delivery.

During the past decades, microdevices have been evaluated as a means to overcome challenges within oral drug delivery, thus improving bioavailability. Fabrication of microdevices is often limited to planar or simple 3D designs. Therefore, this work explores how microscale stereolithography 3D printing can be used to fabricate radiopaque microcontainers with enhanced mucoadhesive geometries, which can enhance bioavailability by increasing gastrointestinal retention. Ex vivo force measurements suggest increased mucoadhesion of microcontainers with adhering features, such as pillars and arrows, compared to a neutral design. In vivo studies, utilizing planar X-ray imaging, show the time-dependent gastrointestinal location of microcontainers, whereas computed tomography scanning and cryogenic scanning electron microscopy reveal information about their spatial dynamics and mucosal interactions, respectively. For the first time, the effect of 3D microdevice modifications on gastrointestinal retention is traced in vivo, and the applied methods provide a much-needed approach for investigating the impact of device design on gastrointestinal retention.

Low-cost, open-source XYZ nanopositioner for high-precision analytical applications.

Nanoscale positioning has numerous applications in both academia and industry. A growing number of applications require devices with long working distances and nanoscale resolutions. Friction-inertia piezoelectric positioners, which are based on the stick-slip mechanism, achieve both nanometer resolution and centimeter-scale travel. However, the requirements of complex preload mechanism, precision machining, and precise assembly increase the cost of conventional friction-inertia nanopositioners. Herein we present the design of an open-source XYZ-axis nanopositioning system. Utilizing a magnet-based stick-slip driving mechanism, the proposed XYZ nanopositioner provides several advantages, including sub-nanometer resolution, a payload capacity of up to 12 kg (horizontal), compact size, low cost, and easy assembly; furthermore, the system is adjustment-free. The performance tests validate the precision of the system in both scanning and stepping operation modes. Moreover, the resonant spectra affirm the rigidity and dynamic response of the mechanism. In addition, we demonstrate the practical applications of this nanopositioner in various measurement techniques, including scanning electron microscopy, vibrometry, and atomic force microscopy. Furthermore, we present 11 variations of the nanopositioner designs that are either compatible with ultra-high-vacuum systems and other existing systems, 3D printable, or hacking commercial linear slides.

Open-source force analyzer with broad sensing range based on an optical pickup unit.

In the pharmaceutical field, oral drug delivery devices continue to shrink down to the micrometer scale, driving a trending demand to investigate ex vivo mucoadhesive force down to the micro-Newton scale. However, owing to the limitation of measuring sensitivity, conventional methods (e.g., a texture analyzer) lack reliability while measuring forces in this range. Herein, we report on an open-source force analyzer that utilizes an optical-pickup-unit (from a DVD player) to detect cantilever-based force transducers and thereby, achieves a wide force-sensing range from 1.1 N to 0.99 nN. The cantilever force transducers can easily be adjusted to fit different force ranges by adjusting the steel shim, magnets, and 3D printed components. To validate the analyzer, we conducted a preliminary study to investigate the effect of time and humidity of mucoadhesion of porcine intestinal tissues. Besides, we measured the mucoadhesive force of a single oral drug delivery microdevice with an average force of 93.7 µN on the top sides of the device. This analyzer offers the possibility of measuring e.g. mucoadhesion of individual microdevices in the micro-Newton range. Hence, the analyzer can assist in the development of miniaturized oral drug delivery devices but has a much wider field of potential force sensing applications.

Open source anaerobic and temperature-controlled in vitro model enabling real-time release studies with live bacteria.

In vitro release and dissolution models are widely used in the development phases of oral drug delivery systems to measure how an active pharmaceutical ingredient (API) is released from a dosage form. However, additional requirements for these models arise when evaluating probiotic dosage forms since they are often sensitive to temperature and oxygen levels. As a solution to this, we propose a custom-designed anaerobic in vitro release setup, made mainly by 3D printing and laser cutting, to function together with state-of-the-art pharmaceutical dissolution equipment - in this case, a microDISS Profiler™. The in vitro release model makes it possible to study the release rate of oxygen-sensitive probiotics in simulated intestinal conditions, while ensuring their survival due to the anaerobic conditions. This has not been possible so far since the available in vitro dissolution models have not been compatible with anaerobic conditions. With two different case studies, the developed model combined with a microDISS Profiler™ has proven capable of measuring the release of a probiotic and a small-molecule API from microdevices for oral drug delivery. Further, the model facilitated the survival of anaerobic bacteria present in the release medium.