4D printing of biodegradable intestinal drug delivery devices with shape-memory effect.

Expanding devices designed to physically facilitate the permeation of drugs across the gastrointestinal mucosa are gaining attention for the oral delivery of therapeutic macromolecules. The ideal system should be biodegradable with latex-like properties, allowing it to withstand gut movement without breaking prematurely and preventing intestinal obstruction or damage. A highly foldable and elastic device is desirable because it can fit into commercial capsules by being compressed into confined spaces.

Extracellular vesicles versus lipid nanoparticles for the delivery of nucleic acids.

Extracellular vesicles (EVs) are increasingly investigated for delivering nucleic acid (NA) therapeutics, leveraging their natural role in transporting NA and protein-based cargo in cell-to-cell signaling. Their synthetic counterparts, lipid nanoparticles (LNPs), have been developed over the past decades as NA carriers, culminating in the approval of several marketed formulations such as patisiran/Onpattro® and the mRNA-1273/BNT162 COVID-19 vaccines. The success of LNPs has sparked efforts to develop innovative technologies to target extrahepatic organs, and to deliver novel therapeutic modalities, such as tools for in vivo gene editing.

Interaction proteomics analysis to provide insight into TFAMoplex-mediated transfection.

In an earlier investigation, our group introduced the TFAMoplex, a transfection agent based on the mitochondrial transcription factor A (TFAM) protein, which complexes DNA into nanoparticles. The original TFAMoplex further contained a bacterial phospholipase to achieve endosomal escape, and the vaccinia-related kinase 1 (VRK1), which significantly boosted the transfection efficiency of the system by an unknown mechanism. This study aims at replacing VRK1 within the TFAMoplex with dynein light chain proteins, specifically RP3, to directly tether the complexes to the dynein motor complex for enhanced cytosolic transport.

Gastrointestinal Permeation Enhancers Beyond Sodium Caprate and SNAC - What is Coming Next?

Oral peptide delivery is trending again. Among the possible reasons are the recent approvals of two oral peptide formulations, which represent a huge stride in the field. For the first time, gastrointestinal (GI) permeation enhancers (PEs) are leveraged to overcome the main limitation of oral peptide delivery-low permeability through the intestinal epithelium.

The intracellular visualization of exogenous DNA in fluorescence microscopy.

In the development of non-viral gene delivery vectors, it is essential to reliably localize and quantify transfected DNA inside the cell. To track DNA, fluorescence microscopy methods are commonly applied. These mostly rely on fluorescently labeled DNA, DNA binding proteins fused to a fluorescent protein, or fluorescence in situ hybridization (FISH).

A Bioinspired and Cost-Effective Device for Minimally Invasive Blood Sampling.

Conventional venipuncture is invasive and challenging in low and middle-income countries. Conversely, point-of-care devices paired with fingersticks, although less invasive, suffer from high variability and low blood volume collection. Recently approved microsampling devices address some of these issues but remain cost-prohibitive for resource-limited settings.

pH-dependent pressure-sensitive colonic capsules for the delivery of aqueous bacterial suspensions.

Microbiome-based therapies hold great promise for treating various diseases, but the efficient delivery of live bacteria to the colon remains a challenge. Furthermore, current oral formulations, such as lyophilized bacterial capsules or tablets, are produced using processes that can decrease bacterial viability. Consequently, high dosages are required to achieve efficacy.

Get out or die trying: Peptide- and protein-based endosomal escape of RNA therapeutics.

RNA therapeutics offer great potential to transform the biomedical landscape, encompassing the treatment of hereditary conditions and the development of better vaccines. However, the delivery of RNAs into the cell is hampered, among others, by poor endosomal escape. This major hurdle is often tackled using special lipids, polymers, or protein-based delivery vectors.

Ultrafast and Controlled Capturing, Loading, and Release of Extracellular Vesicles by a Portable Microstructured Electrochemical Fluidic Device.

Extracellular vesicles (EVs) are secreted by all living cells and are found in body fluids. They exert numerous physiological and pathological functions and serve as cargo shuttles. Due to their safety and inherent bioactivity, they have emerged as versatile therapeutic agents, biomarkers, and potential drug carriers.

Engineering Lipid Spherulites for the Sustained Release of Highly Dosed Small Hydrophilic Compounds.

Currently, there is a lack of parenteral sustained release formulations for the delivery of highly dosed small hydrophilic drugs. Therefore, parenteral lipid spherulites are engineered capable of entrapping large amounts of such compounds and spontaneously releasing them in a sustained fashion. A library of spherulites is prepared with a simple green process, using phosphatidylcholine (PC) and/or phosphatidylethanolamine (PE), nonionic surfactants and water.

3D printing of a controlled urea delivery device for the prevention of tooth decay.

Dental caries is one of the most widespread chronic infectious diseases in the world. It is mainly caused by the production of acid in the biofilm from the bacterial metabolism of carbohydrates. Nowadays, the prevention of caries is mainly based on the use of topical formulations containing fluoride.

Improving extracellular vesicles production through a Bayesian optimization-based experimental design.

With the growing demand and diversity of biological drugs, developing optimal processes for their accelerated production with minimal resource utilization is a pressing challenge. Typically, such optimization involves multiple target properties, such as production yield, biological activity, and product purity. Therefore, strategic experimental design techniques that can characterize the parameter space while simultaneously arriving at the optimal process satisfying multiple target properties are required.

Digital Light 3D Printed Bioresorbable and NIR-Responsive Devices with Photothermal and Shape-Memory Functions.

Digital light processing (DLP) 3D printing is a promising technique for the rapid manufacturing of customized medical devices with high precision. To be successfully translated to a clinical setting, challenges in the development of suitable photopolymerizable materials have yet to be overcome. Besides biocompatibility, it is often desirable for the printed devices to be biodegradable, elastic, and with a therapeutic function.

3D printing of a controlled fluoride delivery device for the prevention and treatment of tooth decay.

Dental decay is a highly prevalent chronic disease affecting people from all ages. Clinically, fluoride supplementation is the primary strategy in the prevention of dental decay. However, the current existing self-application formulations such as gels or mouthwashes are rapidly cleared after administration, resulting in modest efficacy even after repeated applications.

Light-Based Printing of Leachable Salt Molds for Facile Shaping of Complex Structures.

3D printing is a powerful manufacturing technology for shaping materials into complex structures. While the palette of printable materials continues to expand, the rheological and chemical requisites for printing are not always easy to fulfill. Here, a universal manufacturing platform is reported for shaping materials into intricate geometries without the need for their printability, but instead using light-based printed salt structures as leachable molds.