Nanocrystals exhibit significant advantages in improving the oral bioavailability of poorly soluble drugs. However, the complicated absorption properties of nanocrystals and the differences in physiological characteristics between children and adults limit pediatric applications of nanocrystals. To elucidate the absorption differences and the underlying mechanisms between children and adults, the pharmacokinetics and tissue distribution of aprepitant crystals with different particle sizes (NC200, NC500, and MC2.5) in rats and mice at different ages were studied, and their absorption mechanisms were investigated in Caco-2 cells, mice, and rats. It was found that childhood animals demonstrated higher bioavailability compared with adolescent and adult animals, which was related to higher bile salt concentration and accelerated drug dissolution in the intestine of childhood animals. The majority of nanocrystals were dissolved and formed micelles under the influence of bile salts. Compared with intact nanocrystals, the bile salt micelle-associated aprepitant was absorbed through the chylomicron pathway, wherein Apo B assisted in the reassembling of the aprepitant micelles after endocytosis. Higher bile salt concentration and Apo B expression in the intestines of childhood animals are both responsible for the higher chylomicron transport pathways. Elucidation of the chylomicron pathway in the varied absorption of nanocrystals among children, adolescents, and adults provides strong theoretical guidance for promoting the rational and safe use of nanocrystals in pediatric populations.

Microfluidic technology has not been extensively utilized in nanocrystals manufacture, although it has been used in the production of liposomes and LNPs. This is mainly due to concerns including blockage of narrow pipes and corrosion of organic solvents on chips. In this study, a detachable stainless steel microfluidic chip with split-and-recombine (SAR) structure was engraved and used to prepare curcumin nanocrystal suspensions by a microfluidic-antisolvent precipitation method. A simulation study of the mixing activities of three chip structures was conducted by COMSOL Multiphysics software. Then the curcumin nanocrystals preparation was optimized by Box-Behnken design to screen different stabilizers and solvents. Two curcumin nanocrystals formulations with an average particle size of 59.29 nm and 168.40 nm were obtained with PDIs of 0.131 and 0.058, respectively. Compared to curcumin powder, the formulation showed an increase in dissolution rate in 0.1 M HCL while pharmacokinetic study indicated that Cmax was increased by 4.47 and 3.14 times and AUC0-∞ were 4.26 and 3.14 times greater. No clogging or deformation of the chip was observed after long usage. The results demonstrate that the stainless steel microfluidic chips with SAR structure have excellent robustness and controllability. It has the potential to be applied in GMP manufacturing of nanocrystals.

Microscale thermophoresis (MST) is a technique used to measure the strength of molecular interactions. MST is a thermophoretic-based technique that monitors the change in fluorescence associated with the movement of fluorescent-labeled molecules in response to a temperature gradient triggered by an IR LASER. MST has advantages over other approaches for examining molecular interactions, such as isothermal titration calorimetry, nuclear magnetic resonance, biolayer interferometry, and surface plasmon resonance, requiring a small sample size that does not need to be immobilized and a high-sensitivity fluorescence detection. In addition, since the approach involves the loading of samples into capillaries that can be easily sealed, it can be adapted to analyze oxygen-sensitive samples. In this Bio-protocol, we describe the troubleshooting and optimization we have done to enable the use of MST to examine protein-protein interactions, protein-ligand interactions, and protein-nanocrystal interactions. The salient elements in the developed procedures include 1) loading and sealing capabilities in an anaerobic chamber for analysis using a NanoTemper MST located on the benchtop in air, 2) identification of the optimal reducing agents compatible with data acquisition with effective protection against trace oxygen, and 3) the optimization of data acquisition and analysis procedures. The procedures lay the groundwork to define the determinants of molecular interactions in these technically demanding systems. Key features • Established procedures for loading and sealing tubes in an anaerobic chamber for subsequent analysis. • Sodium dithionite (NaDT) could easily be substituted with one electron-reduced 1,1\'-bis(3-sulfonatopropyl)-4,4\'-bipyridinium [(SPr)2V•] to perform sensitive biophysical assays on oxygen-sensitive proteins like the MoFe protein. • Established MST as an experimental tool to quantify binding affinities in novel enzyme-quantum dot biohybrid complexes that are extremely oxygen-sensitive.

Herein, a novel strategy is reported for synthesizing libraries of single crystalline amino acid (AA) nanocrystals with control over size, anisotropy, and polymorphism by leveraging dip-pen nanolithography (DPN) and recrystallization via solvent vapor annealing. The crystals are prepared by first depositing nanoreactors consisting of a solvent with AAs, followed by water vapor-induced recrystallization. This leads to isotropic structures that are non-centrosymmetric with strong piezoelectric (g33 coefficients >1000 mVm N-1), ferroelectric, and non-linear optical properties. However, recrystallizing arrays of isotropic DL-alanine nanodot features with a binary solvent (water and ethanol) leads to arrays of 1D piezoelectric nanorods with their long axis coincident with the polar axis. Moreover, positioning nanoreactors containing AAs (the nanodot features) between micro electrodes leads to capillary formation, making the reactors anisotropic and facilitating piezoelectric nanorod formation between the electrodes. This offers a facile route to device fabrication. These as-fabricated devices respond to ultrasonic stimulation in the form of a piezoelectric response. The technique described herein is significant as it provides a rapid way of investigating non-centrosymmetric nanoscale biocrystals, potentially pivotal for fabricating a new class of stimuli-responsive devices such as sensors, energy harvesters, and stimulators.

Single-photon sources are essential for advancing quantum technologies with scalable integration being a crucial requirement. To date, deterministic positioning of single-photon sources in large-scale photonic structures remains a challenge. In this context, colloidal quantum dots (QDs), particularly core/shell configurations, are attractive due to their solution processability. However, traditional QDs are typically small, about 3 to 6 nm, which restricts their deterministic placement and utility in large-scale photonic devices, particularly within optical cavities. The largest existing core/shell QDs are a family of giant CdSe/CdS QDs, with total diameters ranging from about 20 to 50 nm. Pushing beyond this size limit, we introduce a synthesis strategy for colossal CdSe/CdS QDs, with sizes ranging from 30 to 100 nm, using a stepwise high-temperature continuous injection method. Electron microscopy reveals a consistent hexagonal diamond morphology composed of 12 semipolar {101̅1} facets and one polar (0001) facet. We also identify conditions where shell growth is disrupted, leading to defects, islands, and mechanical instability, which suggest synthetic requirements for growing crystalline particles beyond 100 nm. The stepwise growth of thick CdS shells on CdSe cores enables the synthesis of emissive QDs with long photoluminescence lifetimes of a few microseconds and suppressed blinking at room temperature. Notably, QDs with 80 and 100 CdS monolayers exhibit high single-photon emission purity with second-order photon correlation g(2)(0) values below 0.2.

Grazing incidence small angle X-ray scattering (GISAXS) was used to study the structure and interparticle spacing of monolayers of organic ligand-stabilized iron oxide nanocrystals floating at the air-water interface on a Langmuir trough, and after transfer to a solid support via the Langmuir-Blodgett technique. GISAXS measurements of the nanocrystal arrangement at the air-water interface showed that lateral compression decreased the interparticle spacing of continuous films. GISAXS also revealed that Langmuir-Blodgett transfer of the nanocrystal layers to a silicon substrate led to a stretching of the film, with a significant increase in interparticle spacing.

OBJECTIVE: The objective of the present case study was to increase the exposure of the poorly soluble crystalline compound A.
METHODS: Mice received 10 mg/kg of crystalline compound A formulated in eight different cosolvent, oil, and cyclodextrin mixtures.
RESULTS: In all cases, AUC0-24h and maximum blood/plasma concentration (Cmax) were in the range of 6-16 µM × h and <1.4 µm, respectively, with a bioavailability below 18%. When 6% cremophor (CrEL) was added to three selected vehicles, AUC0-24h and Cmax increased ~5-10 times. The obtained pharmacokinetic profile of the most improved formulation using CrEL was possible to superimpose on the one obtained after administration of a CrEL-free amorphous solid dispersion (ASD, HPMC-AS:drug, 80:20) suspension of compound A.
CONCLUSIONS: It is crucial to find an optimal screen vehicle as early as possible for a poorly water-soluble lead series and then avoid time and resource-consuming vehicle testing of multiple compounds in vivo. An ASD approach is more suited for clinical development when more time and resources are allocated to the project. In this case study, some preclinical formulations were used to maximize exposure but also as preindicators for ASDs later in the development chain.

The steady rheological behavior of suspensions of solid particles thickened by cellulose nanocrystals is investigated. Two different types and sizes of particles are used in the preparation of suspensions, namely, TG hollow spheres of 69 µm in Sauter mean diameter and solospheres S-32 of 14 µm in Sauter mean diameter. The nanocrystal concentration varies from 0 to 3.5 wt% and the particle concentration varies from 0 to 57.2 vol%. The influence of salt (NaCl) concentration and pH on the rheology of suspensions is also investigated. The suspensions generally exhibit shear-thinning behavior. The degree of shear-thinning is stronger in suspensions of smaller size particles. The experimental viscosity data are adequately described by a power-law model. The variations in power-law parameters (consistency index and flow behavior index) under different conditions are determined and discussed in detail.

Many brain diseases pose serious challenges to human life. Alzheimer\'s Disease (AD) and Parkinson\'s Disease (PD) are common neurodegenerative diseases that seriously threaten human health. Glioma is a common malignant tumor. However, drugs cannot cross physiological and pathological barriers and most therapeutic drugs cannot enter the brain because of the presence of the Blood-brain Barrier (BBB) and Blood- -brain Tumor Barrier (BBTB). How to enable drugs to penetrate the BBB to enter the brain, reduce systemic toxicity, and penetrate BBTB to exert therapeutic effects has become a challenge. Nanosuspension can successfully formulate drugs that are difficult to dissolve in water and oil by using surfactants as stabilizers, which is suitable for the brain target delivery of class II and IV drugs in the Biopharmaceutical Classification System (BCS). In nanosuspension drug delivery systems, the physical properties of nanostructures have a great impact on the accumulation of drugs at the target site, such as the brain. Optimizing the physical parameters of the nanosuspension can improve the efficiency of brain drug delivery and disease treatment. Therefore, the key challenges, influencing factors, and future perspectives of nanosuspension in enhancing brain drug delivery are summarized and reviewed here. This article aims to provide a better understanding of nanosuspension formulation technology used for brain delivery and strategies used to overcome various physiological barriers.

The strong ligand effect in B-doped Pd-based (PdB) catalysts renders them a promising anode for constructing formic acid fuel cells (FAFCs) exhibiting high power density and outstanding stability. However, the enhancement of the oxidation barrier is unavoidable in this alloy system owing to the electron transfer (ET) from B to Pd. In this study, a hydrogen doping strategy is employed to open charge freedom in PdB compounds and boost their formic acid oxidation reaction (FAOR) activity by suppressing the ET process. The resulting hydrogen-doped PdB (PdBH) exhibits an ultrahigh mass activity of up to 1.2A mg-1 Pd, which is 3.23 times that of the PdB catalyst and 9.55 times that of Pd black. Detailed experimental and theoretical studies show that the interstitial hydrogen leads to enhanced orbital hybridization and reduced electron density around Pd. This optimized ligand effect weakens the carbon monoxide adsorption and increases the direct pathway preference of PdBH, resulting in its outstanding catalytic activity for the FAOR. The development of this high-performance hydrogen-doped PdB catalyst is an important step toward the construction of advanced light element co-doped metal catalysts.