3D printed multi-compartment capsular devices for two-pulse oral drug delivery

In the drug delivery area, versatile therapeutic systems intended to yield customized combinations of drugs, drug doses and release kinetics have drawn increasing attention, especially because of the advantages that personalized pharmaceutical treatments would offer. In this respect, a previously proposed capsular device able to control the release performance based on its design and composition, which could extemporaneously be filled, was improved to include multiple separate compartments so that differing active ingredients or formulations may be conveyed. The compartments, which may differ in thickness and composition, resulted from assembly of two hollow halves through a joint also acting as a partition. The systems were manufactured by fused deposition modeling (FDM) 3D printing, which holds special potential for product personalization, and injection molding (IM) that would enable production on a larger scale. Through combination of compartments having wall thickness of 600 or 1200\u3bcm, composed of promptly soluble, swellable/erodible or enteric soluble polymers, devices showing two-pulse release patterns, consistent with the nature of the starting materials, were obtained. Systems fabricated using the two techniques exhibited comparable performance, thus proving the prototyping ability of FDM versus IM

Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling

Fused deposition modeling (FDM) is a 3D printing technique based on the deposition of successive layers of thermoplastic materials following their softening/melting. Such a technique holds huge potential for the manufacturing of pharmaceutical products and is currently under extensive investigation. Challenges in this field are mainly related to the paucity of adequate filaments composed of pharmaceutical grade materials, which are needed for feeding the FDM equipment. Accordingly, a number of polymers of common use in pharmaceutical formulation were evaluated as starting materials for fabrication via hot melt extrusion of filaments suitable for FDM processes. By using a twin-screw extruder, filaments based on insoluble (ethylcellulose, Eudragit\uae RL), promptly soluble (polyethylene oxide, Kollicoat\uae IR), enteric soluble (Eudragit\uae L, hydroxypropyl methylcellulose acetate succinate) and swellable/erodible (hydrophilic cellulose derivatives, polyvinyl alcohol, Soluplus\uae) polymers were successfully produced, and the possibility of employing them for printing 600 \u3bcm thick disks was demonstrated. The behavior of disks as barriers when in contact with aqueous fluids was shown consistent with the functional application of the relevant polymeric components. The produced filaments were thus considered potentially suitable for printing capsules and coating layers for immediate or modified release, and, when loaded with active ingredients, any type of dosage forms

Clinical‐epidemiological aspects of the Monkeypox 2022 epidemic: a multicenter study by the Italian SIDeMaST Group of Sexually Transmitted, Infectious and Tropical Diseases

Dear Editor,In spring 2022, an increase of monkeypox (mpox) cases was reported in Europe. Mpox is a zoonotic virus of the Poxviridae family, is endemic in the Congo Basin and just few cases outside Africa were reported before 2022. Its cutaneous presentation is similar to smallpox, usually preceded by a prodromal phase of fever, lymphadenopathy, headache and asthenia. Infection can occur through various means, including skin-to-skin contact, respiratory droplets or contact with fomites. The new outbreak is unique due to the increased human-to-human transmission, without an animal reservoir, particularly among men who have sex with men (MSM). As of February 13, 2023, 85.860 confirmed cases have been reported in 110 countries

Bcl-2-regulated cell death signalling in the prevention of autoimmunity

Cell death mediated through the intrinsic, Bcl-2-regulated mitochondrial apoptosis signalling pathway is critical for lymphocyte development and the establishment of central and maintenance of peripheral tolerance. Defects in Bcl-2-regulated cell death signalling have been reported to cause or correlate with autoimmunity in mice and men. This review focuses on the role of Bcl-2 family proteins implicated in the development of autoimmune disorders and their potential as targets for therapeutic intervention

Series viscoelastic actuators can match human force perception

Series elastic actuators (SEAs) are frequently used for force control in haptic interaction, because they decouple actuator inertia from the end effector by a compliant element. This element is usually a metal spring or beam, where the static force-deformation relationship offers a cheap force sensor. For high-precision force control, however, the remaining small inertia of this elastic element and of the end effector still limit the sensing performance and rendering transparency. Here, we extend the concept to deformable end effectors manufactured of viscoelastic materials. These materials offer the advantage of extremely low mass at high maximum deformation and applicable load. However, force and deformation are no longer statically related, and history of force and deformation has to be accounted for. We describe an observer-based solution, which allows drift-free force measurement with high accuracy and precision. Although the description of the viscoelastic behavior involves higher-order derivatives, the proposed observer does not require any numerical differentiation. This new integrated concept of sensing and actuation, called series viscoelastic actuator (SVA), is applied to our high-precision haptic device OSVALD, which is targeted at perception experiments that require sensing and rendering of forces in the range of the human tactile threshold. User-device interaction force is controlled using state-of-the-art control strategies of SEAs. Force estimation and force control performance are evaluated experimentally and prove to be compatible with the intended applications, showing that SVAs open up new possibilities for the use of series compliance and damping in high-precision haptic interfaces