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Oral delivery of proteins and peptides is one of the main challenges in pharmaceutical drug development. Microdevices have the possibility to protect the therapeutics until release is desired, avoiding losses by degradation. One type of microdevice is polymeric microcontainers. In this study, lysozyme is chosen as model protein and loaded into microcontainers with the permeation enhancer sodium decanoate (C10). The loaded microcontainers are sealed and functionalized by applying polymeric lids onto the cavity of the devices. The first lid is poly(lactic-co-glycolic) acid (PLGA) and on top of this either polyethylene glycol (PEG) or chitosan is applied (PLGA+PEG or PLGA+chitosan, respectively). The functionalization is evaluated in vitro for morphology, drug release, and mucoadhesive properties. These are coupled with in vitro and ex vivo studies using Caco-2 cells, Caco-2/HT29-MTX-E12 co-cultures, and porcine intestinal tissue. PLGA+chitosan shows slower release compared to PLGA+PEG or only PLGA in buffer and the transport of lysozyme across cell cultures is not enhanced compared to the bulk powder. Microcontainers coated with chitosan or PEG demonstrate a three times stronger adhesion during ex vivo mucoadhesion studies compared to samples without coatings. Altogether, functionalized microcontainers with mucoadhesive properties and tunable release for oral protein delivery are developed and characterized.
Text 24 3D printing technology is widely employed in various scientific disciplines as well as 25 industrial applications such as hearing aid manufacturing. While technological advances and 26 increasing resolution are making 3D printing accessible for microfabrication purposes, one 27 question remains: how can small and delicate components like micro gears, lattices or micro 28 medical devices be released from the build surface of the 3D printer without manual 29 intervention? Herein, a method for 3D printing on top of water-soluble sacrificial substrates 30 made from polyvinyl alcohol (PVA) is presented. Pre-fabricated sacrificial PVA substrates 31 can be mounted onto a customized holder and serve as build surface during the 3D printing 32 operation. The substrates do not only facilitate a mild release of 3D printed objects after 33 dissolution of the sacrificial material, they also potentially allow for a convenient 34 manipulation and further array-based processing of pre-determined patterns of printed 35 structures subsequent to the 3D printing procedure. This, in turn, may enable a full integration 36 into automated production lines. The fabrication of PVA substrates is thoroughly 37
Conventional photopolymerization-based 3D printing still requires developing a concise and cost-effective method to improve the printing resolution at the nanoscale. Here, we propose the use of a gaming console optical drive pickup unit for 3D photopolymerization. This mass-produced optical pickup unit features a finely adjustable diode laser, allowing us to adjust the printing resolution from tens of micrometres down to hundreds of nanometres without requiring oxygen radical scavenging or costly femtosecond lasers. We evaluate the 3D printing performance using a commercial photopolymer under different laser exposure parameters. The proposed printing system achieves a resolution of 385 nm along the lateral direction and XYZ nano-resolution linear stages enable a printing volume of up to 50 × 50 × 25 mm3. Finally, we demonstrate the fabrication of 3D stereoscopic microstructures. The substantially simplified optics proposed here paves the way for affordable high-resolution micro/nanoscale 3D fabrication.
With the growing popularity and application of microfabricated devices in oral drug delivery (ODD), masking technologies for drug loading and surface modification become highly relevant. Considering the speed of design and fabrication processes and the necessity for continuous iterations of e.g. the shape and sizes of the devices during the optimization process, there is a need for adaptable, precise and low-cost masking techniques. Here, a novel method is presented for masking ODD microdevices, namely microcontainers, using the physical characteristics of polydimethylsiloxane (PDMS). When compared to a rigid microfabricated shadow mask, used for filling drugs in microcontainers, the PDMS masking technique allows more facile and precise loading of higher quantities of an active compound, without the need of alignment. The method provides flexibility and is adjustable to devices fabricated from different materials with various geometries, topologies and sizes. This userfriendly flexible masking method overcomes the limitations of other masking techniques and is certainly not limited to ODD and is recommended for a wide range of microdevices.
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