Oral delivery of porous starch-loaded bilayer microgels for controlled drug delivery and treatment of ulcerative colitis.

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 formulations 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.

Construction of redox-sensitive liposomes modified by glycyrrhetinic acid and evaluation of anti-hepatocellular carcinoma activity.

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.

Pseudo Polyampholytes with Sensitively Ion-Responsive Conformational Transition Based on Positively Charged Host-Guest Complexes.

Biological polyampholytes are ubiquitous in living organisms with primary functions including serving as transporters for moving chemical molecular species across the cell membranes. Synthetic amphoteric macromolecules that can change their phase states depending on the environment to simulate some properties of natural polyampholytes are of great interest. Here, the implementation of synthetic pseudo polymeric ampholytes is explored with ion-recognition-triggered conformational change. The phase transition behaviors of the ion-recognition-creative polyampholytes that contain deprotonated carboxylic acid groups as negative charges and 18-crown-6 units for forming positively charged host-guest complexes are systematically investigated. The ion-recognition-triggered phase transition behaviors of pseudo polyampholytes significantly depend on cation species and concentrations. Only those specific ions such as K+ , Ba2+ , Sr2+ and Pb2+ ions that can form 1:1 host-guest complexes with 18-crown-6 units in polymers enable control over conformational change like that of traditional pH-dependent polyampholytes. By regulating the content of carboxylic acid groups to match the content of ion-recognized positive charges provided by the host-guest complexes, the pseudo polyampholytes are more sensitive to the recognizable cations. Such ion-recognition-triggered amphoteric characteristics make the pseudo polyampholytes act like biological proteins, nucleic acids, and enzymes as molecular transporters, genetic code storage, and biocatalysts in artificial systems.

Exploration of the Adsorption Kinetics of Surfactants at the Water-Oil Interface via Grand-Canonical Molecular Dynamics Simulations.

It is well-known that surfactants tend to aggregate into clusters or micelles in aqueous solutions due to their special structures, and it is difficult for the surfactant molecules involved in the aggregation to move spontaneously to the oil-water interface. In this article, we developed a new grand-canonical molecular dynamics (GCMD) model to predict the saturated adsorption amount of surfactant with constant concentration of surfactant molecules in the bulk phase, which can prevent surfactants aggregating in the bulk phase and get the atomic details of the interfacial structural change with increase of the adsorption amount through a single GCMD run. The adsorption of anionic surfactant sodium dodecyl sulfate (SDS) at the heptane-water interface was studied to validate the model. The saturated adsorption amount obtained from the GCMD simulation is consistent with the experimental results. The adsorption kinetics of SDS molecules during the simulation can be divided into three stages: linear adsorption stage, transition adsorption stage, and dynamic equilibrium stage. We also carried out equilibrium molecular dynamics (EMD) simulations to compare with GCMD simulation. This GCMD model can effectively reduce the simulation time with correct prediction of the interfacial saturation adsorption. We believe the GCMD method could be especially helpful for the computational study of surfactant adsorption under complex environments or emulsion systems with the adsorption of multiple types of surfactants.

Complete plastid genome of Primula calliantha Franch. (Primulaceae): an alpine ornamental plant endemic to Hengduan Mountain, China.

Primula calliantha Franch. is an alpine species with an ornamental value that is endemic to the Hengduan Mountains of southwest China. Here, we sequenced and assembled its plastid complete genome, which is a circular molecule of 151,954 bp and contains a large single-copy (83,820 bp) and a small single-copy (17,814 bp) region, separated by a pair of inverted repeats (25,160 bp). There are 131 genes, 86 protein-coding, 37 tRNAs, and 8 rRNAs in the plastome, of which 114 genes, 80 CDSs, 30 tRNAs, and 4 rRNAs are unique, respectively. The P. calliantha plastid genome shows a high level of synteny with its close relatives, P. chionantha, P. purdomii, and P. woodwardii. Phylogenetic analysis based on 60 complete chloroplast genomes of Primulaceae confirmed its delimitation in Primula.