Tailored Polymersomes for Enhanced Oral Drug Delivery: pH-Sensitive Systems for Intestinal Delivery of Immunosuppressants.

Ensuring precise drug release at target sites is crucial for effective treatment. Here, pH-responsive nanoparticles for oral administration of mycophenolate mofetil, an alternative therapy for patients with inflammatory bowel disease unresponsive to conventional treatments is developed. However, its oral administration presents challenges due to its low solubility in the small intestine and high solubility and absorption in the stomach. Therefore, this aim is to design a drug delivery system capable of maintaining drug solubility compared to the free drug while delaying absorption from the stomach to the intestine. Successful synthesis and assembly of a block copolymer incorporating a pH-responsive functional group is achieved. Dynamic light scattering indicated a significant change in hydrodynamic size when the pH exceeded 6.5, confirming successful incorporation of the pH-responsive group. Encapsulation and controlled release of mycophenolate mofetil are efficiently demonstrated, with 90% release observed at intestinal pH. In vitro cell culture studies confirmed biocompatibility, showing no toxicity or adverse effects on Caco-2 cells. In vivo oral rat studies indicated reduced drug absorption in the stomach and enhanced absorption in the small intestine with the developed formulation. This research presents a promising drug delivery system with potential applications in the treatment of inflammatory bowel disease.

Evaluation of the SERS performances of Tabun and VX label-free detection in complex and multicomponent fluids.

Nerve agents represent a serious threat to security worldwide. Chemical terrorism has become an alarming danger since the technological progresses have simplified the production of nerve agents. Therefore, there is an immediate demand for a fast and precise detection of these compounds on-site and real-time. In this perspective, Surface-Enhanced Raman Scattering (SERS) has emerged as a well-suited alternative for on-field detection. SERS performances of unfunctionalized SERS substrates were evaluated in realistic samples. Two nerve agents, Tabun and VX, were diluted in two matrix models: a contact lens solution, and a caffeine-based eye serum. The performance two research-grade instruments and two portable devices were compared. Despite the use of a small sampling volume of complex matrices without any sample pre-treatment, we achieved Tabun detection in both media, with a practical limit of detection (LOD) in the range of 7-9 ppm in contact lens liquid, and of 10.2 ppm in eye serum. VX detection turned out to be more challenging and was achieved only in contact lens solution, with a practical LOD in the range of 0.6-5 ppm. These results demonstrate the feasibility of on-field detection of nerve agents with SERS, that could be implemented when there is suspicion of chemical threat.

Fully Biodegradable Elastomer-Based Device for Oral Macromolecule Delivery.

Oral devices, such as foil-type devices, show great potential for the delivery of poorly permeable macromolecules by enabling unidirectional release of the loaded pharmaceutical composition in close proximity to the epithelium in the small intestine or colon. However, one of the primary concerns associated with the use of foil-type devices so far has been the utilization of nonbiodegradable elastomers in the fabrication of the devices. Therefore, research into biodegradable substitute materials with similar characteristics enables drug delivery in a sustainable and environmentally friendly manner. In this study, a biodegradable elastomer, polyoctanediol citrate (POC), was synthesized via a one-pot reaction, with subsequent purification and microscale pattern replication via casting. The microstructure geometry was designed to enable fabrication of foil-type devices with the selected elastomer, which has a high intrinsic surface free energy. The final elastomer was demonstrated to have an elastic modulus ranging up to 2.2 ± 0.1 MPa, with strain at failure up to 110.1 ± 1.5%. Devices were loaded with acetaminophen and enterically coated, demonstrating 100% release at 2.5 h, following dissolution for 1 h in 0.1 M hydrochloric acid and 1.5 h in pH 6.8 phosphate-buffered saline. The elastomer demonstrated promising properties based on mechanical testing, surface free energy evaluation, and degradation studies.

High-yield fabrication of monodisperse multilayer nanofibrous microparticles for advanced oral drug delivery applications.

Recent advances in the use of nano- and microparticles in drug delivery, cell therapy, and tissue engineering have led to increasing attention towards nanostructured microparticulate formulations for maximum benefit from both nano- and micron sized features. Scalable manufacturing of monodisperse nanostructured microparticles with tunable size, shape, content, and release rate remains a big challenge. Current technology, mainly comprises complex multi-step chemical procedures with limited control over these aspects. Here, we demonstrate a novel technique for high-yield fabrication of monodisperse monolayer and multilayer nanofibrous microparticles (MoNami and MuNaMi respectively). The fabrication procedure includes sequential electrospinning followed by micro-cutting at room temperature and transfer of particles for collection. The big advantage of the introduced technique is the potential to apply several polymer-drug combinations forming multilayer microparticles enjoying extracellular matrix (ECM)-mimicking architecture with tunable release profile. We demonstrate the fabrication and study the factors affecting the final three-dimensional structure. A model drug is encapsulated into a three-layer sheet (PLGA-pullulan-PLGA), and we demonstrate how the release profile changes from burst to sustain by simply cutting particles out of the electrospun sheet. We believe our fabrication method offers a unique and facile platform for realizing advanced microparticles for oral drug delivery applications.

Optics miniaturization strategy for demanding Raman spectroscopy applications.

Raman spectroscopy provides non-destructive, label-free quantitative studies of chemical compositions at the microscale as used on NASA's Perseverance rover on Mars. Such capabilities come at the cost of high requirements for instrumentation. Here we present a centimeter-scale miniaturization of a Raman spectrometer using cheap non-stabilized laser diodes, densely packed optics, and non-cooled small sensors. The performance is comparable with expensive bulky research-grade Raman systems. It has excellent sensitivity, low power consumption, perfect wavenumber, intensity calibration, and 7 cm-1 resolution within the 400-4000 cm-1 range using a built-in reference. High performance and versatility are demonstrated in use cases including quantification of methanol in beverages, in-vivo Raman measurements of human skin, fermentation monitoring, chemical Raman mapping at sub-micrometer resolution, quantitative SERS mapping of the anti-cancer drug methotrexate and in-vitro bacteria identification. We foresee that the miniaturization will allow realization of super-compact Raman spectrometers for integration in smartphones and medical devices, democratizing Raman technology.

Flexible Coatings Facilitate pH-Targeted Drug Release via Self-Unfolding Foils: Applications for Oral Drug Delivery.

Ingestible self-configurable proximity-enabling devices have been developed as a non-invasive platform to improve the bioavailability of drug compounds via swellable or self-unfolding devices. Self-unfolding foils support unidirectional drug release in close proximity to the intestinal epithelium, the main drug absorption site following oral administration. The foils are loaded with a solid-state formulation containing the active pharmaceutical ingredient and then coated and rolled into enteric capsules. The coated lid must remain intact to ensure drug protection in the rolled state until targeted release in the small intestine after capsule disintegration. Despite promising results in previous studies, the deposition of an enteric top coating that remains intact after rolling is still challenging. In this study, we compare different mixtures of enteric polymers and a plasticizer, PEG 6000, as potential coating materials. We evaluate mechanical properties as well as drug protection and targeted release in gastric and intestinal media, respectively. Commercially available Eudragit® FL30D-55 appears to be the most suitable material due to its high strain at failure and integrity after capsule fitting. In vitro studies of coated foils in gastric and intestinal media confirm successful pH-triggered drug release. This indicates the potential advantage of the selected material in the development of self-unfolding foils for oral drug delivery.