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Pharmaceutical nanosuspensions are formed when drug crystals are suspended in aqueous media in the presence of stabilizers. This technology offers a convenient way to enhance the dissolution of poorly water-soluble drug compounds. The stabilizers exert their action through electrostatic or steric interactions, however, the molecular requirements of stabilizing agents have not been studied extensively. Here, four structurally related amphiphilic Janus-dendrimers were synthesized and screened to determine the roles of different macromolecular domains on the stabilization of drug crystals. Physical interaction and nanomilling experiments have substantiated that Janus-dendrimers with fourth generation hydrophilic dendrons were superior to third generation analogues and Poloxamer 188 in stabilizing indomethacin suspensions. Contact angle and surface plasmon resonance measurements support the hypothesis that Janus-dendrimers bind to indomethacin surfaces via hydrophobic interactions and that the number of hydrophobic alkyl tails determines the adsorption kinetics of the Janus-dendrimers. The results showed that amphiphilic Janus-dendrimers adsorb onto drug particles and thus can be used to provide steric stabilization against aggregation and recrystallization. The modular synthetic route for new amphiphilic Janus-dendrimers offers, thus, for the first time a versatile platform for stable general-use stabilizing agents of drug suspensions.
Pharmaceutical nanosuspensions are formed when drug crystals are suspended in aqueous media in the presence of stabilizers. This technology offers a convenient way to enhance the dissolution of poorly water-soluble drug compounds. The stabilizers exert their action through electrostatic or steric interactions, however, the molecular requirements of stabilizing agents have not been studied extensively. Here, four structurally related amphiphilic Janusdendrimers were synthesized and screened to determine the roles of different macromolecular domains on the stabilization of drug crystals. Physical interaction and nanomilling experiments have substantiated that Janus-dendrimers with fourth generation hydrophilic dendrons were superior to third generation analogues and Poloxamer 188 in stabilizing indomethacin suspensions. Contact angle and surface plasmon resonance measurements support the hypothesis that Janus-dendrimers bind to indomethacin surfaces via hydrophobic interactions and that the number of hydrophobic alkyl tails determines the adsorption kinetics of the Janus-dendrimers. The results showed that amphiphilic Janus-dendrimers adsorb onto drug particles, and thus can be used to provide steric stabilization against aggregation and recrystallization. The modular synthetic route for new amphiphilic Janus-dendrimers offers thus, for the first time, a versatile platform for stable general-use stabilizing agents of drug suspensions.
The design of antimicrobial surfaces as integral parts of advanced biomaterials is nowadays a high research priority, as the accumulation of microorganisms on surfaces inflicts substantial costs on the health and industry sectors. At present, there is a growing interest in designing functional materials from polymers abundant in nature, such as cellulose, that combine sustainability with outstanding mechanical properties and economic production. There is also the need to find suitable replacements for antimicrobial silver-based agents due to environmental toxicity and spread of resistance to metal antimicrobials. Herein we report the unprecedented decoration of cellulose nanofibril (CNF) films with dehydroabietylamine 1 (CNF-CMC-1), to give an innovative contact-active surface active against Gram-positive and Gram-negative bacteria including the methicillin-resistant S. aureus MRSA14TK301, with low potential to spread resistance and good biocompatibility, all achieved with low surface coverage. CNF-CMC-1 was particularly effective against S. aureus ATCC12528, causing virtually complete reduction of the total cells from 10 5 colony forming units (CFU)/mL bacterial suspensions, after 24 h of contact. This gentle chemical modification of the surface of CNF fully retained the beneficial properties of the original film, including moisture buffering and strength, relevant in many potential applications. Our originally designed surface represents a new class of ecofriendly biomaterials that optimizes the performance of CNF by adding antimicrobial properties without the need for environmentally toxic silver.
Bacterial biofilm infections incur massive costs on healthcare systems worldwide. Particularly worrisome are the infections associated with pressure ulcers and prosthetic, plastic, and reconstructive surgeries, where staphylococci are the major biofilm-forming pathogens. Non-leaching antimicrobial surfaces offer great promise for the design of bioactive coatings to be used in medical devices. However, the vast majority are cationic, which brings about undesirable toxicity. To circumvent this issue, we have developed antimicrobial nanocellulose films by direct functionalization of the surface with dehydroabietic acid derivatives. Our conceptually unique design generates non-leaching anionic surfaces that reduce the number of viable staphylococci in suspension, including drug-resistant Staphylococcus aureus, by an impressive 4-5 log units, upon contact. Moreover, the films clearly prevent bacterial colonization of the surface in a model mimicking the physiological environment in chronic wounds. Their activity is not hampered by high protein content, and they nurture fibroblast growth at the surface without causing significant hemolysis. In this work, we have generated nanocellulose films with indisputable antimicrobial activity demonstrated using state-of-the-art models that best depict an "in vivo scenario". Our approach is to use fully renewable polymers and find suitable alternatives to silver and cationic antimicrobials.
Human-robot object handover is a key skill for the future of human-robot collaboration. CORSMAL 2020 Challenge focuses on the perception part of this problem: the robot needs to estimate the filling mass of a container held by a human. Although there are powerful methods in image processing and audio processing individually, answering such a problem requires processing data from multiple sensors together. The appearance of the container, the sound of the filling, and the depth data provide essential information. We propose a multi-modal method to predict three key indicators of the filling mass: filling type, filling level, and container capacity. These indicators are then combined to estimate the filling mass of a container. Our method obtained Top-1 overall performance among all submissions to CORSMAL 2020 Challenge on both public and private subsets while showing no evidence of overfitting. Our source code is publicly available: github.com/v-iashin/CORSMAL.
StyleGAN2 is a Tensorflow-based Generative Adversarial Network (GAN) framework that represents the state-of-the-art in generative image modelling. The current release of StyleGAN2 implements multi-GPU training via Tensorflow’s device contexts which limits data parallelism to a single node. In this work, a data-parallel multi-node training capability is implemented in StyleGAN2 via Horovod which enables harnessing the compute capability of larger cluster architectures. We demonstrate that the new Horovod-based communication outperforms the previous context approach on a single node. Furthermore, we demonstrate that the multi-node training does not compromise the accuracy of StyleGAN2 for a constant effective batch size. Finally, we report strong and weak scaling of the new implementation up to 64 NVIDIA Tesla A100 GPUs distributed across eight NVIDIA DGX A100 nodes, demonstrating the utility of the approach at scale.