Pharmaceutical Analysis of Protein-Peptide Coformulations and the Influence of Polysorbates.

Coformulation is an approach to formulating multiple biopharmaceutical therapeutics in a single formulation, promising the benefits of both therapies in one dose. However, as molecular stability is a key consideration in traditional biopharmaceutical formulations, stability of coformulations will require extensive investigation. This study evaluated the effects of traditional formulation stabilizers, specifically surfactants, at different grades, namely, regular grade (RG) Tween 20 and Tween 80 and Super-refined Polysorbate 20 and 80.

Tailoring the release of highly loaded amorphous solid dispersions via additive manufacturing.

In the last decades, tremendous improvements have been made in enhancing the bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Lately, their customisation potential has become a reality through filament-based 3D-printing (3DP). Highly loaded oral amorphous solid dispersions (ASDs) are of particular interest, since they drastically reduce the pill burden.

Miniaturized High-Throughput Amorphous Solid Dispersion Screening via Picoliter Volume 2D-Inkjet Printing of Formulation Microarrays.

Many new drug substances exhibit poor physicochemical properties and therefore require significant time and material resources to develop into safe and efficacious medicinal products. This typically involves exploring a large amount of compositional space and may require excessive amounts of drug compounds, which may not be adequate at the early stage of drug development. Scaled-down screening methods have been used as a cost-effective approach to the early-stage formulation.

Exploiting Online Spatially Resolved Dynamic Light Scattering and Flow-NMR for Automated Size Targeting of PISA-Synthesized Block Copolymer Nanoparticles.

Programmable synthesis of polymer nanoparticles prepared by polymerization-induced self-assembly (PISA) mediated by reversible addition-fragmentation chain-transfer (RAFT) dispersion polymerization with specified diameter is achieved in an automated flow-reactor platform. Real-time particle size and monomer conversion is obtained via inline spatially resolved dynamic light scattering (SRDLS) and benchtop nuclear magnetic resonance (NMR) instrumentation. An initial training experiment generated a relationship between copolymer block length and particle size for the synthesis of poly(,-dimethylacrylamide)--poly(diacetone acrylamide) (PDMAm--PDAAm) nanoparticles.

Optical mapping of ground reaction force dynamics in freely behaving larvae.

During locomotion, soft-bodied terrestrial animals solve complex control problems at substrate interfaces, but our understanding of how they achieve this without rigid components remains incomplete. Here, we develop new all-optical methods based on optical interference in a deformable substrate to measure ground reaction forces (GRFs) with micrometre and nanonewton precision in behaving larvae. Combining this with a kinematic analysis of substrate-interfacing features, we shed new light onto the biomechanical control of larval locomotion.

Using a systematic and quantitative approach to generate new insights into drug loading of PLGA nanoparticles using nanoprecipitation.

The synthesis of drug-loaded PLGA nanoparticles through nanoprecipitation in solvent/antisolvent mixtures is well reported but lacks clarity in explaining drug loading mechanisms and the prediction of efficiency of drug entrapment. Various methods using physical parameters such as log and solid-state drug-polymer solubility aim to predict the intensity of drug-polymer interactions but lack precision. In particular, the zero-enthalpy method for drug/polymer solubility may be intrinsically inaccurate, as we demonstrate.

Deformable microlaser force sensing.

Mechanical forces are key regulators of cellular behavior and function, affecting many fundamental biological processes such as cell migration, embryogenesis, immunological responses, and pathological states. Specialized force sensors and imaging techniques have been developed to quantify these otherwise invisible forces in single cells and in vivo. However, current techniques rely heavily on high-resolution microscopy and do not allow interrogation of optically dense tissue, reducing their application to 2D cell cultures and highly transparent biological tissue.

Wireless magnetoelectrically powered organic light-emitting diodes.

Compact wireless light sources are a fundamental building block for applications ranging from wireless displays to optical implants. However, their realization remains challenging because of constraints in miniaturization and the integration of power harvesting and light-emission technologies. Here, we introduce a strategy for a compact wirelessly powered light-source that consists of a magnetoelectric transducer serving as power source and substrate and an antiparallel pair of custom-designed organic light-emitting diodes.

The positive-negative-competence (PNC) model of psychological responses to representations of robots.

Robots are becoming an increasingly prominent part of society. Despite their growing importance, there exists no overarching model that synthesizes people's psychological reactions to robots and identifies what factors shape them. To address this, we created a taxonomy of affective, cognitive and behavioural processes in response to a comprehensive stimulus sample depicting robots from 28 domains of human activity (for example, education, hospitality and industry) and examined its individual difference predictors.

Selecting Counterions to Improve Ionized Hydrophilic Drug Encapsulation in Polymeric Nanoparticles.

Hydrophobic ion pairing (HIP) can successfully increase the drug loading and control the release kinetics of ionizable hydrophilic drugs, addressing challenges that prevent these molecules from reaching the clinic. Nevertheless, polymeric nanoparticle (PNP) formulation development requires trial-and-error experimentation to meet the target product profile, which is laborious and costly. Herein, we design a preformulation framework (solid-state screening, computational approach, and solubility in PNP-forming emulsion) to understand counterion-drug-polymer interactions and accelerate the PNP formulation development for HIP systems.

Predicting attitudinal and behavioral responses to COVID-19 pandemic using machine learning.

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions.

Spore exines increase vitamin D clinical bioavailability by mucoadhesion and bile triggered release.

Sporopollenin exine capsules (SpECs) are microcapsules derived from the outer shells (exines) of plant spore and pollen grains. This work reports the first clinical study on healthy volunteers to show enhanced bioavailability of vitamin D encapsulated in SpECs from Lycopodium clavatum L. spore grains vs vitamin D alone, and the first evidence (in vitro, ex vivo and in vivo) of mechanisms to account for the enhancement and release of the active in the small intestine.

Predicting spinel solid solutions using a random atom substitution method.

Exploration of chemical composition and structural configuration space is the central problem in crystal structure prediction. Even in limiting structure space to a single structure type, many different compositions and configurations are possible. In this work, we attempt to address this problem using an extension to the existing ChemDASH code in which variable compositions can be explored.

National identity predicts public health support during a global pandemic.

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g.

Local practices and production confer resilience to rural Pacific food systems during the COVID-19 pandemic.

Resilience of food systems is key to ensuring food security through crisis. The COVID-19 pandemic presents an unprecedented shock that reveals varying levels of resilience of increasingly interconnected food systems across the globe. We contribute to the ongoing debate about whether increased connectivity reduces or enhances resilience in the context of rural Pacific food systems, while examining how communities have adapted to the global shocks associated with the pandemic to ensure food security.

Amorphous solid dispersions: Utilization and challenges in preclinical drug development within AstraZeneca.

The poor aqueous solubility of many active pharmaceutical ingredients (APIs) dominates much of the early drug development portfolio and poses a major challenge in pharmaceutical development. Polymer-based amorphous solid dispersions (ASDs) are becoming increasingly common and offer a promising formulation strategy to tackle the solubility and oral absorption issues of these APIs. This review discusses the design, manufacture, and utilisation of ASD formulations in preclinical drug development, with a key focus on the pre-formulation assessments and workflows employed at AstraZeneca.

Simulation of protein pulling dynamics on second time scale with boxed molecular dynamics.

We demonstrate how recently developed Boxed Molecular Dynamics (BXD) and kinetics [D. V. Shalashilin et al.

Real-time imaging of cellular forces using optical interference.

Important dynamic processes in mechanobiology remain elusive due to a lack of tools to image the small cellular forces at play with sufficient speed and throughput. Here, we introduce a fast, interference-based force imaging method that uses the illumination of an elastic deformable microcavity with two rapidly alternating wavelengths to map forces. We show real-time acquisition and processing of data, obtain images of mechanical activity while scanning across a cell culture, and investigate sub-second fluctuations of the piconewton forces exerted by macrophage podosomes.

Inexpensive Methods for Live Imaging of Central Pattern Generator Activity in the Larval Locomotor System.

Central pattern generators (CPGs) are neural networks that produce rhythmic motor activity in the absence of sensory input. CPGs produce 'fictive' behaviours which parallel activity seen in intact animals. CPG networks have been identified in a wide variety of model organisms and have been shown to be critical for generating rhythmic behaviours such as swimming, walking, chewing and breathing.

Mechanical Unfolding of Proteins-A Comparative Nonequilibrium Molecular Dynamics Study.

Mechanical signals regulate functions of mechanosensitive proteins by inducing structural changes that are determinant for force-dependent interactions. Talin is a focal adhesion protein that is known to extend under mechanical load, and it has been shown to unfold via intermediate states. Here, we compared different nonequilibrium molecular dynamics (MD) simulations to study unfolding of the talin rod.

Prognostic value of multiparametric magnetic resonance imaging, transient elastography and blood-based fibrosis markers in patients with chronic liver disease.

Background & Aims: Liver cT , liver T , transient elastography (TE) and blood-based biomarkers have independently been shown to predict clinical outcomes but have not been directly compared in a single cohort of patients. Our aim was to compare these tests' prognostic value in a cohort of patients with compensated chronic liver disease.

Methods: Patients with unselected compensated liver disease aetiologies had baseline assessments and were followed up for development of clinical outcomes, blinded to the imaging results.