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Nanotechnological approaches for efficient N2B delivery: from small-molecule drugs to biopharmaceuticals

Central nervous system diseases negatively affect patients and society. Providing successful noninvasive treatments for these diseases is challenging because of the presence of the blood–brain barrier. While protecting the brain’s homeostasis, the barrier limits the passage of almost all large-molecule drugs and most small-molecule drugs. A noninvasive method, nose-to-brain delivery (N2B delivery) has been proposed to overcome this challenge. By exploiting the direct anatomical interaction between the nose and the brain, the drugs can reach the target, the brain. Moreover, the drugs can be encapsulated into various drug delivery systems to enhance physicochemical characteristics and targeting success. Many preclinical data show that this strategy can effectively deliver biopharmaceuticals to the brain. Therefore, this review focuses on N2B delivery while giving examples of different drug delivery systems suitable for the applications. In addition, we emphasize the importance of the effective delivery of monoclonal antibodies and RNA and stress the recent literature tackling this challenge. While giving examples of nanotechnological approaches for the effective delivery of small or large molecules from the current literature, we highlight the preclinical studies and their results to prove the strategies’ success and limitations.

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A biomimetic approach towards a universal slippery liquid infused surface coating.

One biomimetic approach to surface passivation involves a series of surface coatings based on the slick surfaces of carnivorous pitcher plants (Nepenthes), termed slippery liquid-infused porous surfaces (SLIPS). This study introduces a simplified method to produce SLIPS using a polydopamine (PDA) anchor layer, inspired by mussel adhesion. SLIPS layers were formed on cyclic olefin copolymer, silicon, and stainless steel substrates, by first growing a PDA film on each substrate. This was followed by a hydrophobic liquid anchor layer created by functionalizing the PDA film with a fluorinated thiol. Finally, perfluorodecalin was applied to the surface immediately prior to use. These biomimetic surface functionalization steps were confirmed by several complimentary surface analysis techniques. The wettability of each surface was probed with water contact angle measurements, while the chemical composition of the layer was determined by X-ray photoelectron spectroscopy. Finally, ordering of specific chemical groups within our PDA SLIPS layer was determined via sum frequency generation spectroscopy. The hemocompatibility of our new PDA-based SLIPS coating was then evaluated by tracking FXII activation, fibrin generation time, clot morphology, and platelet adhesion to the surface. This hemocompatibility work suggests that PDA SLIPS coatings slow or prevent clotting, but the observation of both FXII activation and the presence of adherent and activated platelets at the PDA SLIPS samples imply that this formulation of a SLIPS coating is not completely omniphobic.

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Nanoarchitectonics with cetrimonium bromide on metal nanoparticles for linker-free detection of toxic metal ions and catalytic degradation of 4-nitrophenol.

Heavy metal ions and organic pollutants, such as 4-nitrophenol (4-NP), pose significant environmental and human health threats. Addressing these challenges necessitates using advanced nanoparticle-based systems capable of efficient detection and degradation. However, conventional approaches utilizing strong capping agents like cetrimonium bromide (CTAB) on nanoparticles lead to limitations due to the rigid nature of CTAB. This restricts its utility in heavy metal detection and 4-NP degradation, requiring additional surface modifications using linker molecules, thereby increasing process complexity and cost. To overcome these limitations, there is a critical need for the development of an easy-to-use, dual-functional, linker-free nanosystem capable of simultaneous detection of heavy metals and efficient degradation of 4-NP. For enabling linker-free/ligand-free detection of heavy metal ions and catalytic degradation of 4-NP, CTAB was engineered as a versatile capping agent on gold and silver nanoparticles. Various factors, including nanoparticle characteristics such as shape, size, metal composition, centrifugation, and NaOH amount, were investigated for their impact on the performance of CTAB-capped nanoparticles in heavy metal detection and 4-NP degradation. CTAB-Au nanospheres demonstrated limited heavy metal ion detection capability but exhibited remarkable efficiency in degrading 94.37% of 4-NP within 1 min. In contrast, silver nanospheres effectively detected Hg2+, Cu2+, and Fe3+ at concentrations as low as 1 ppm and degraded 90.78% of 4-NP within 30 min. Moreover, anisotropic gold nanorods (CTAB-AuNR1 and CTAB-AuNR2) showed promising sensing capabilities towards Cu2+, Cr3+, and Hg2+ at 0.5 OD, while efficiently degrading 4-NP within 5 min at 1 OD. This study emphasizes the importance of tailoring parameters of CTAB-capped nanoparticles for specific sensing and catalytic applications, offering potential solutions for environmental remediation and human health protection.

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Interaction of graphene oxide with tannic acid: computational modeling and toxicity mitigation in C. elegans.

Graphene oxide (GO) undergoes multiple transformations when introduced to biological and environmental media. GO surface favors the adsorption of biomolecules through different types of interaction mechanisms, modulating the biological effects of the material. In this study, we investigated the interaction of GO with tannic acid (TA) and its consequences for GO toxicity. We focused on understanding how TA interacts with GO, its impact on the material surface chemistry, colloidal stability, as well as, toxicity and biodistribution using the Caenorhabditis elegans model. Employing computational modeling, including reactive classical molecular dynamics and ab initio calculations, we reveal that TA preferentially binds to the most reactive sites on GO surfaces via the oxygen-containing groups or the carbon matrix; van der Waals interaction forces dominate the binding energy. TA exhibits a dose-dependent mitigating effect on the toxicity of GO, which can be attributed not only to the surface interactions between the molecule and the material but also to the inherent biological properties of TA in C. elegans. Our findings contribute to a deeper understanding of GO's environmental behavior and toxicity and highlight the potential of tannic acid for the synthesis and surface functionalization of graphene-based nanomaterials, offering insights into safer nanotechnology development.

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