Probiotics regulate intestinal flora balance and enhance the intestinal barrier, which is useful in preventing and treating colitis. However, they have strict storage requirements. In addition, they degrade in a strongly acidic environment, resulting in a significant decrease in their activity when used as microbial agents. Lactobacillus rhamnosus GG (LGG) was loaded into acid-resistant and colon-targeting double-layer microgels. The inner layer consists of guar gum (GG) and low methoxyl pectin (LMP), which can achieve retention and degradation in the colon. To achieve colon localization, the outer layer was composed of chitosan (CS) and sodium alginate (SA). The formulation demonstrated favorable bio-responses across various pH conditions in vitro and sustained release of LGG in the colon lesions. Bare LGG survival decreased by 52.2 % in simulated gastric juice (pH 1.2) for 2 h, whereas that of encapsulated LGG decreased by 18.5 %. In the DSS-induced inflammatory model, LGGloaded microgel significantly alleviated UC symptoms in mice and reduced inflammatory factor levels in the colon. Encapsulation of LGG improved its stability in acidic conditions, thus increasing its content at the colon lesions and reducing pathogenic bacteria. These findings provide an experimental basis and a technical reference for developing and applying probiotic microgel preparations.

Hydrogels have been widely used in wound dressings owing to their biocompatibility and bacteriostatic properties. In this study, a chitosan‐citric acid gel film was prepared using chitosan as the raw material and citric acid as the acid solvent and cross‐linking agent. In addition, to increase the antibacterial effect of the gel film, ketoconazole/β‐cyclodextrin inclusion complex was prepared by inclusion technology and added to the gel film to prepare a chitosan‐citric acid sustained‐release gel film loaded with ketoconazole/β‐cyclodextrin inclusion complex for treating cutaneous candidiasis. The physical and chemical properties of the chitosan‐citric acid gel films were investigated using infrared spectroscopy, x‐ray diffraction, water vapor transmittance test, thermal analysis, and swelling tests. Drug release, antibacterial, and toxicity tests of the chitosan‐citric acid gel film loading with ketoconazole/β‐cyclodextrin inclusion complex were carried out in vitro. The composite film showed good sustained drug release behavior, antibacterial effects, and biocompatibility in vitro. These results support that the chitosan‐citric acid hydrogel has great potential as a gel wound dressing for the treatment of cutaneous candidiasis.

We prepared one type of bilayer microgels for oral administration with three effects: pH responsiveness, time lag, and colon enzyme degradation. Combined with the dual biological effects of curcumin (Cur) for reducing inflammation and promoting repair of colonic mucosal injury, targeted colonic localization and release of Cur according to the colonic microenvironment were enhanced. The inner core, derived from guar gum and low-methoxyl pectin, afforded colonic adhesion and degradation behavior; the outer layer, modified by alginate and chitosan via polyelectrolyte interaction, achieved colonic localization. The porous starch (PS)-mediated strong adsorption allowed Cur loading in inner core to achieve a multifunctional delivery system. In vitro, the formulations exhibited good bioresponses at different pH conditions, potentially delaying Cur release in the upper gastrointestinal tract. In vivo, dextran sulfate sodium-induced ulcerative colitis (UC) symptoms were significantly alleviated after oral administration, accompanied by reduced levels of inflammatory factors. The formulations facilitated colonic delivery, allowing Cur accumulation in colonic tissue. Moreover, the formula-tions could alter gut microbiota composition in mice. During Cur delivery, each formulation increased species richness, decreased pathogenic bacterial content, and afforded synergistic effects against UC. These PS-loaded bilayer microgels, exhibiting excellent biocompatibility, multi-bioresponsiveness, and colon targeting, could be beneficial in UC therapy, allowing development into a novel oral formulation.

Correction for 'Mechanochemical asymmetric three-component Mannich reaction involving unreactive arylamines' by Xiaoyun Hu et al., Org. Biomol. Chem., 2023, https://doi.org/10.1039/d3ob00954h.

The aim of this study was to construct a bifunctional liposome with hepatic-targeting capacity by modifying with a targeting ligand and an intracellular tumor reduction response functional group to deliver drugs precisely to focal liver tissues and release them in large quantities in hepatocellular carcinoma cells. This could improve drug efficacy and reduce toxic side effects at the same time. First, the bifunctional ligand for liposome was successfully obtained by chemically synthesizing it from the hepatic-targeting glycyrrhetinic acid (GA) molecule, cystamine, and the membrane component cholesterol. Then the ligand was used to modify the liposomes. The particle size, PDI and zeta potential of the liposomes were determined with a nanoparticle sizer, and the morphology was observed by transmission electron microscopy. The encapsulation efficiency and drug release behavior were also determined. Further, the stability in vitro of the liposomes and the changes in the simulated reducing environment were determined. Finally, the antitumor activity in vitro and cellular uptake efficiency of the drug-loaded liposomes were investigated by performing cellular assays. The results showed that the prepared liposomes had a uniform particle size of 143.6 ± 2.86 nm with good stability and an encapsulation rate of 84.3 ± 2.1 %. Moreover, the particle size of the liposomes significantly increased and the structure was destroyed in a DTT reducing environment. Cellular experiments showed that the modified liposoes had better cytotoxic effects on hepatocarcinoma cells than both normal liposomes and free drugs. This study has great potential for tumor therapy and provides novel ideas for the clinical use of oncology drugs in dosage forms.

Currently, conventional chemotherapy for hepatocellular carcinoma is limited and has serious side effects due to premature release and limited lesion targeting recognition. In this study, to further address the challenges of drug delivery for liver cancer, a novel hybrid lipid–polymer nanocomposite, glycyrrhetinic acid-modified lipogel (GA-SS-LG), was designed to merge the beneficial features of both polymer-based and lipid-based delivery systems in a single nanocarrier, which was proposed as a liposome with a bifunctional ligand as well as a polymer gel core inside in the liposome. The inhibitory effect of the GA-SS-LG on HepG2 cells was studied in vitro by using curcumin (Cur) as a model drug. The experimental results show that the incorporation of the polymer gel core improved the stability of the liposomes and had the ability to enhance drug encapsulation and delay drug release. At the same time, the liposome outer membrane could be modified with functional ligands to deliver drugs accurately. Our system accurately delivers drugs to tumor cells and responds quickly to release the loaded drugs in large quantities. This study improves the antitumor activity of Cur by preparing a lipogel composite system and provides a new formulation that combines both the polymer-based and lipid-based delivery systems in a single nanocarrier for the clinical application of antitumor drugs.

A novel and practical method for the synthesis of (2S,2′S)-3,3,3′,3′-tetraaryl-2,2′-bioxiranes from natural tartaric acid has been developed. Four-step synthetic protocol includes the following steps: esterification of tartaric acid, arylation of tartaric esters, highly regioselective 2,3-cyclosulfitation, 1,4-chlorination of (2R,3R)-1,1,4,4-tetraarylbutanetetraols with thionyl chloride, and intramolecular cyclization reaction. It was confirmed that no stereochemical inversion of the chirogenic centers upon preparation of bioxirane derivatives takes place. Further methodology of the catalyst-free regiospecific transformation to enantiopure 1,3-oxazoline-2-thione derivatives has successfully been developed by coupling the bioxiranes with NH4SCN, which provides a new and facile access to different TADDOL derivatives.

Anti-inflammatory drugs for ulcerative colitis (UC) treatment should specifically penetrate and accumulate in the colon tissue. Herein, a multi-bioresponsive anti-inflammatory drug (curcumin, CUR)-loaded heterogeneous double-membrane microgels (CUR@microgels) for oral administration was fabricated in this study, in which the inner core was derived from polyvinyl alcohol (PVA) and guar gum (GG) and the outer gel was decoration with alginate and chitosan by polyelectrolyte interactions. The structure and morphology of microgels were characterized. In vitro, the formulation exhibited good bio-responses at different pH conditions and sustained-release properties in simulated colon fluid with a drug-release rate of 84.6 % over 34 h. With the assistance of the outlayer gels, the microgels effectively delayed the premature drug release of CUR in the upper gastrointestinal tract. In vivo studies revealed that CUR@microgels specifically accumulated in the colon tissue for 24 h, which suggest that the interlayer gels were apt to reach colon lesion. As expected, the oral administration of microgels remarkably alleviated the symptoms of UC and protected the colon tissue in DSS-induced UC mice. The above results indicated that these facilely fabricated microgels which exhibited excellent biocompatibility and multi-bioresponsive drug release, had an apparent effect on the treatment of UC, which represents a promising drug delivery strategy for CUR in a clinical application.

Hypericum hengshanense is a previously uninvestigated endemic plant species of China. Three new aclyphloroglucinols, hengshanols A-C (1-3), and two new geranyl-α-pyrones, hengshanpyol D and E (4 and 5), together with three known compounds were isolated from the aerial parts of H. hengshanense. The structure of these compounds were elucidated by NMR, MS, optical rotation, and ECD data. All compounds were isolated from H. hengshanense for the first time. Among them, compounds 2-4 may have anti-laryngeal cancer activity. Compounds isolated were tested for glucose uptake in L6 cells, and compound 4 showed the most potent glucose uptake with 1.62-fold enhancement.

A major drawback of oral treatment of inflammatory bowel disease (IBD) is the non-specific distribution of drugs during long-term treatment. Despite its effectiveness as an anti-inflammatory drug, curcumin (CUR) is limited by its low bioavailability in IBD treatment. Herein, a pH-sensitive composite hyaluronic acid/gelatin (HA/GE) hydrogel drug delivery system containing carboxymethyl chitosan (CC) microspheres loaded with CUR was fabricated for IBD treatment. The composition and structure of the composite system were optimized and the physicochemical properties were characterized using infrared spectroscopy, X-ray diffraction, swelling, and release behavior studies. In vitro, the formulation exhibited good sustained release property and the drug release rate was 65% for 50 h. In vivo pharmacokinetic experiments indicated that high level of CUR was maintained in the colon tissue for more than 24 h; it also played an anti-inflammatory role by evaluating the histopathological changes through hematoxylin and eosin (H&E), myeloperoxidase (MPO), and immunofluorescent staining. Additionally, the formulation substantially inhibited the level of the main pro-inflammatory cytokines of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) secreted by macrophages, compared to the control group. The pharmacodynamic experiment showed that the formulation group of CUR@gels had the best therapeutic effect on colitis in mice. The composite gel delivery system has potential for the effective delivery of CUR in the treatment of colitis. This study also provides a reference for the design and preparation of a new oral drug delivery system with controlled release behavior.

A new double-layer, pH-sensitive, composite hydrogel sustained-release system based on polysaccharides and synthetic polymers with combined functions of different inner/outer hydrogels was prepared. The polysaccharides inner core based on sodium alginate (SA) and carboxymethyl cellulose (CMC), was formed by physical crosslinking with pH-sensitive property. The synthetic polymer out-layer with enhanced stability was introduced by chemical crosslinking to eliminate the expansion of inner core and the diffusion of inner content. The physicochemical structure of the double-layer hydrogels was characterized. The drug-release results demonstrated that the sustained-release effect of the hydrogels for different model drugs could be regulated by changing the composition or thickness of the hydrogel layer. The significant sustained-release effect for BSA and indomethacin indicated that the bilayer hydrogel can be developed into a novel sustained delivery system for bioactive substance or drugs with potential applications in drugs and functional foods.