Enhanced Photocatalytic Activity of V2C MXene-Coupled ZnO Porous Nanosheets with Increased Surface Area and Effective Charge Transfer.

Photocatalysis performs excellently when degrading organic pollutants, but the photocatalytic degradation rate is not high for most photocatalysts due to their narrow sunlight adsorption range and high recombination rate of electron hole pairs. Herein, we use V2C-MXene with a wide sunlight adsorption range to couple ZnO porous nanosheets and form ZnO/MXene hybrids using a facile electrostatic self-assembly method. The ZnO/MXene hybrids acquired demonstrated improved photochemical efficiency in breaking down methylene blue (MB) when contrasted with porous ZnO nanosheets. The degradation rate of MB reached 99.8% under UV irradiation for 120 min after the ZnO/MXene hybrid formation, while 38.6% was attained by the ZnO porous nanosheets. Moreover, photodegradation rate constants (k) were calculated as 3.05 × 10-3 and 5.42 × 10-2 min-1 for ZnO porous nanosheets and ZnO/MXene hybrids, respectively, indicating that the photodegradation performance was enhanced by 17.8 times after the modification of V2C. This was probably because the modification of V2C can increase the specific surface area to provide more sites for MB adsorption, widen the sunlight adsorption range to produce good photothermal effect, and facilitate the transfer of photogenerated carriers in ZnO to promote the reaction of more photogenerated carriers with MB. Hence, this work offers a simple approach to creating effective photocatalysts for breaking down organic contaminants.

Flash Fabrication of Orally Targeted Nanocomplexes for Improved Transport of Salmon Calcitonin across the Intestine.

Salmon calcitonin (sCT) is a potent calcium-regulating peptide hormone and widely applied for the treatment of some bone diseases clinically. However, the therapeutic usefulness of sCT is hindered by the frequent injection required, owing to its short plasma half-life and therapeutic need for a high dose. Oral delivery is a popular modality of administration for patients because of its convenience to self-administration and high patient compliance, while orally administered sCT remains a great challenge currently due to the existence of multiple barriers in the gastrointestinal (GI) tract. Here, we introduced an orally targeted delivery system to increase the transport of sCT across the intestine through both the paracellular permeation route and the bile acid pathway. In this system, sCT-based glycol chitosan-taurocholic acid conjugate (GC-T)/dextran sulfate (DS) ternary nanocomplexes (NC-T) were produced by a flash nanocomplexation (FNC) process in a kinetically controlled mode. The optimized NC-T exhibited well-controlled properties with a uniform and sub-60 nm hydrodynamic diameter, high batch-to-batch reproducibility, good physical or chemical stability, as well as sustained drug release behaviors. The studies revealed that NC-T could effectively improve the intestinal uptake and permeability, owing to its surface functionalization with the taurocholic acid ligand. In the rat model, orally administered NC-T showed an obvious hypocalcemia effect and a relative oral bioavailability of 10.9%. An in vivo assay also demonstrated that NC-T induced no observable side effect after long-term oral administration. As a result, the orally targeted nanocomplex might be a promising candidate for improving the oral transport of therapeutic peptides.

Augmenting Therapeutic Potential of Polyphenols by Hydrogen-Bonding Complexation for the Treatment of Acute Lung Inflammation.

Dysregulated inflammation is considered as an essential pathological process in inflammation-associated diseases, which would be aggravated by high levels of reactive oxygen species (ROS) generation inducing oxidative stress. Currently, extensive attention has been paid to polyphenolic compounds owing to their broad spectrum biological activities, such as antioxidant and anti-inflammatory effects, while their therapeutic potential has been compromised by the poor stability, short plasma half-life, and low bioavailability. Given that polyphenols have a wide range of structural characteristics and various physicochemical properties, there remains a real challenge toward green, mass production of universal nanocarriers for effective entrapment of these active pharmaceutical ingredients. In this study, we adopted a flash nanocomplexation (FNC) platform to prepare nanocomplexes comprising polyphenols and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) enabled by hydrogen bonding. We confirmed that the molecular structure of polyphenols has a great influence on their complexation with TPGS, and stable nanocomplexes were formed when the number of phenolic hydroxyl groups of polyphenols was above the value of 8. These hydrogen-bonded nanocomplexes produced by an FNC apparatus exhibited well-controlled quality with uniform size, good colloidal stability, and high batch-to-batch repeatability, thus improving the druggability as potent nanotherapeutics for antioxidant and anti-inflammatory applications. In vivo experiments indicated that the optimal nanocomplex (EGCG-NC) can be applied to ameliorate acute lung injury in a mice model after nasal administration. These results proved that polyphenols formulated with TPGS for nanocomplex formation through hydrogen-bonding complexation could augment their therapeutic potential for modulating hyperactive inflammation in the treatment of acute lung inflammation.

Scalable Manufacturing of Enteric Encapsulation Systems for Site-Specific Oral Insulin Delivery.

Oral drug delivery is a more favored mode of administration because of its ease of administration, high patient compliance, and low healthcare costs. However, no oral protein formulations are commercially available currently due to hostile gastrointestinal (GI) barriers resulting in insignificant oral bioavailability of macromolecular drugs. Herein, we used insulin as a model protein drug; insulin-loaded N-(2-hydroxy)-propyl-3-trimethylammonium chloride modified chitosan (HTCC)/sodium tripolyphosphate (TPP) nanocomplex (NC) as a nanocore was further encapsulated into enteric Eudragit L100-55 material, through a two-step flash nanocomplexation (FNC) process in a reliable and scalable manner, forming our NC-in-Eudragit composite particles (NE). Particle size and surface properties of our optimized NE were tailored to protect the loaded insulin from acidic degradation in the hostile stomach environment and to achieve intestinal site-specific drug release as well as the improvement of oral delivery efficiency of insulin. In addition, the oral administration of the optimized NE to type 1 diabetic rats could induce a very significant hypoglycemic effect with a relative oral bioavailability of 13.3%. Our results demonstrated that enteric encapsulation of nanotherapeutics using a FNC apparatus could cause drug formulations to possess better size controllability, batch-mode reproducibility, and homogeneous surface coating and then significantly enhance their oral bioavailability of insulin, indicating its great potential for clinical translation of oral protein therapeutics.