Wei Li

Skin wound infection has become a notable medical threat. Herein, the polysaccharide-based injectable hydrogels with multifunctionality were developed by a simple and fast gelation process not only to inactivate bacteria but also to accelerate bacteria-infected wound healing. Sodium nitroprusside (SNP) loaded PCN-224 nanoparticles were introduced into the polymer matrix formed by the dynamic and reversible coordinate bonds between Ag⁺ with carboxyl and amino or hydroxyl groups on carboxymethyl chitosan (CMCS), hydrogen bonds and electrostatic interactions in the polymer to fabricate SNP@PCN@Gel hydrogels. SNP@PCN@Gel displayed interconnected porous structure, excellent self-healing capacity, low cytotoxicity, good blood compatibility, and robust antibacterial activity. SNP@PCN@Gel could produce reactive oxygen species (ROS) and NO along with Fe²⁺, and showed long-term sustained release of Ag⁺, thereby effectively killing bacteria by synergistic photothermal (hyperthermia), photodynamic (ROS), chemodynamic (Fenton reaction), gas (NO) and ion (Ag⁺ and -NH₃⁺ in CMCS) therapy. Remarkably, the hydrogels significantly promoted granulation tissue formation, reepithelization, collagen deposition and angiogenesis as well as wound contraction in bacteria-infected wound healing. Taken together, the strategy represented a general method to engineer the unprecedented photoactivatable “all-in-one” hydrogels with enhanced antibacterial activity and paved a new way for development of antibiotic alternatives and wound dressing. Graphical abstract

A self-sufficient bifunctional enzyme integrating reductive amination and coenzyme regeneration activities was developed and successfully employed to synthesize (S)-cyclopropylglycine with an improved reaction rate 2.1-fold over the native enzymes and a short bioconversion period of 6 h at a high substrate concentration of 120 g·L⁻¹ and space–time yield of (S)-cyclopropylglycine up to 377.3 g·L⁻¹·d⁻¹, higher than that of any previously reported data. Additionally, (S)-cyclopropylglycine could be continuously synthesized for 90 h with the enzymes packed in a dialysis tube, providing 634.6 g of (S)-cyclopropylglycine with >99.5% ee and over 95% conversion yield up to 12 changes. These results confirmed that the newly developed NADH-driven biocatalytic system could be utilized as a self-sufficient biocatalyst for industrial application in the synthesis of (S)-cyclopropylglycine, which provides a chiral center and cyclopropyl fragment for the frequent synthesis of preclinical/clinical drug molecules.

The development of amorphous solid dispersions (ASD) is one way to overcome the bioavailability challenges of poorly water-soluble drug. Herein, Curcumin (CUR) was dispersed in the polymeric matrix of Eudragit^®E100 by solvent evaporation, giving ASD, donated as CUR@Eudragit^®E100. Solubility and stability of CUR were greatly enhanced. DSC and XRD analysis confirmed that the incorporated CUR was present in an amorphous state. The interaction between CUR and Eudragit^®E100 was investigated through FTIR and molecular modelling studies which implied that -OH groups in CUR, and carboxyl and amino groups in Eudragit^®E100 involved in the hydrogen bond formation. High resolution atomic force microscopy was employed to directly visualize the molecular morphology of Eudragit^®E100 and CUR in CUR@Eudragit^®E100 and the interaction between CUR and the polymer. pH influenced CUR release profile in which the sustained release pattern was revealed vs the physical mixtures. From the plasma concentration vs time profile graph, oral bioavailability of Cur@Eudragit^®E100 was approximately 5-fold higher than that of native CUR. These results confirmed the potential of designing ASD to enhance the solubility and bioavailability of CUR, simultaneously deliver CUR through this alternative administration route. Graphical Abstract

The Cin-Pt( iv )-Val prodrug exerts more effective anti-tumor activities in vitro and in vivo than cisplatin by a synergistic mechanism involving DNA damage and inhibition of HDAC and MMP-2 and 9 activities.

Enzymes are biocatalysts. In this study, a novel biocatalyst consisting of magnetic combined cross-linked enzyme aggregates (combi-CLEAs) of 3-quinuclidinone reductase (QNR) and glucose dehydrogenase (GDH) for enantioselective synthesis of (R)-3-quinuclidinolwith regeneration of cofactors in situ was developed. The magnetic combi-CLEAs were fabricated with the use of ammonium sulfate as a precipitant and glutaraldehyde as a cross-linker for direct immobilization of QNR and GDH from E. coli BL(21) cell lysates onto amino-functionalized Fe₃O₄ nanoparticles. The physicochemical properties of the magnetic combi-CLEAs were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and magnetic measurements. Field emission scanning electron microscope (FE-SEM) images revealed a spherical structure with numerous pores which facilitate the movement of the substrates and coenzymes. Moreover, the magnetic combi-CLEAs exhibited improved operational and thermal stability, enhanced catalytic performance for transformation of 3-quinuclidinone (33 g/L) into (R)-3-quinuclidinol in 100% conversion yield and 100% enantiomeric excess (ee) after 3 h of reaction. The activity of the biocatalysts was preserved about 80% after 70 days storage and retained more than 40% of its initial activity after ten cycles. These results demonstrated that the magnetic combi-CLEAs, as cost-effective and environmentally friendly biocatalysts, were suitable for application in synthesis of (R)-3-quinuclidinol essential for the production of solifenacin and aclidinium with better performance than those currently available.

The environmental risk from antibiotics is an issue of increasing concern. So, carboxymethyl β-cyclodextrin-functionalized montmorillonite nanosheets were for the first time successfully synthesized through a cheap, environmentally friendly and scalable approach and confirmed by FTIR, XRD and TGA. FE-SEM investigation showed that the resulting functional material could be further self-assembled into dense supramolecular organoclay networks (D-networks). The antibacterial properties of the D-networks loaded with natural berberine hydrochloride (BBH) were investigated toward E. coli and S. aureus by using colony growth on agar plates, bacterial growth curves based on optical densities, and confocal and fluorescence microscopy. Our studies demonstrated that the BBH loaded D-network antibacterial activity was concentration dependent and significantly exceeded that of free BBH. FE-SEM observation confirmed that E. coli and S. aureus can directly contact the D-networks and confocal and fluorescence microscopy showed that free BBH was only very poorly internalized, while the BBH released from the BBH-loaded D-network could be internalized efficiently into bacterial cells, resulting in an increment of the intracellular BBH level compared with the free BBH group. Time-dependent antibacterial activity was observed and it was found that the BBH-loaded D-network dispersion at the BBH dosage of 600 μg mL⁻¹ almost completely suppressed the growth of E. coli, leading to a viability loss of up to 98.45 ± 1.22%, while the BBH-loaded D-network dispersion at the BBH concentration of 250 μg mL⁻¹ exhibited a growth inhibition of 97.81 ± 0.83% toward S. aureus over three days. Our results suggest that supramolecular organoclay networks, in the future, may function as promising antibacterial drug carrier systems to promote BBH delivery in E. coli and S. aureus, which can reduce the environmental risk of antibiotics.

Background: Humanized recombinant endostatin (rh-endostatin, Sulijia®) is an inhibitor of tumor angiogenesis. We aimed to assess efficacy and safety of rh-endostatin or placebo with vinorelbine/cisplatin (NP) as first-line treatment for patients with advanced non-small cell lung cancer (NSCLC).

Objectives: Baicalin (BCL) has potential therapeutic benefits, but its clinical outcomes are restricted mainly because of low water solubility. This study sought to improve the water solubility of BCL by the formation of inclusion complex with β-cyclodextrin (β-CD). Methods: The inclusion complex was studied by solubility test, differential scanning calorimeter (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), 1H Nuclear magnetic resonance (1HNMR) and scanning electron microscopy (SEM). Molecular docking was conducted to verify the experimental findings. The dissolution rate was determined by dialysis membrane method. In vivo absorption studies in rats were conducted and high-performance liquid chromatography (HPLC) was used to analyse the plasma level of BCL after oral administration. Key findings: The DSC, FTIR, XRD, 1HNMR and SEM findings suggested the formation of inclusion complex between BCL and β-CD in 1 : 1 stoichiometry. Molecular docking demonstrated the insertion of benzene ring of BCL into β-CD cavity by hydrophobic interactions and possible H-bond formation. Moreover, β-CD markedly improved the solubility of BCL and displayed AL-type phase diagrams. The improvement in dissolution rate of the inclusion complex was reflected in the earlier Tmax, higher Cmax and larger AUC0–t than that of BCL after oral administration. Conclusions: β-cyclodextrin complex can be used as an effective formulation strategy for development of BCL-loaded delivery system with better therapeutic outcomes.