Poly(2-ethyl-2-oxazoline) (PEOz), a hydrophilic long-chain polymer synthesized by living cationic ring-opening isomerization polymerization of 2-ethyl-2-oxazoline, has the characteristics of low toxicity, biocompatibility, flexible chain, and modified expediently. PEOz is a potential substitute of polyethylene glycol (PEG) to render the ability of long-circulation, enhance cellular uptake and endosomal escape behaviors to PEOz modified drug delivery system. In this review, we summarized recent literature for the research progress of physicochemical properties, synthetic methods and the application of PEOz in drug delivery system.

To study the substances in fudosteine, one synthetic by-product and five forced degradation products were detected by hydrophilic interaction chromatography (HILIC). Quadrupole-time-of-flight mass spectrometry (Q-TOF MS) was used for accurate mass determination and product ion scanning. Five related substances were identified in the products of mass spectra fragmentations elucidation, and verified further according to synthetic process and stress testing results. The results obtained are valuable for fudosteine manufacturing process control and quality assurance.

Fluorescent polystyrene nanospheres (PS) were used to explore the impact of substrate stiffness on cell uptake of nanoparticles in the breast cancer cells. Polyacrylamide (PAA) gels with varying stiffness were prepared by photopolymerization, and type Ⅰ rat tail collagen was covalently conjugated on the surface of PAA gels to facilitate cell adhesion. Type Ⅰ rat tail collagen was also used to fabricate collagen gels for 3D cell culture. Cells of human breast cancer cell line MCF-7 were incubated in the 2D culture on PAA gels and 3D culture within collagen gels. Next, nanospheres of 20 nm and 50 nm polystyrene were applied to MCF-7 cells in the 2D or 3D cultures. Cell morphology and uptake efficiency were observed with confocal microscopy. Our study demonstrates that substrate stiffness differentially regulated the cell morphology as well as the cell uptake behavior of polystyrene nanospheres in MCF-7 cells under 2D or 3D culture conditions.

With the extracts of Puerariae Lobatae Radix as the research object, the moisture absorption isotherm at 298, 308 and 318 K was determined through dynamic water vapor adsorption. Moisture absorption isotherm models were applied to the simulation of moisture absorption behavior. The enthalpy, entropy and Gibbs free energy for moisture adsorption were calculated according to the model and the enthalpy-entropy compensation was used to analysis moisture adsorption process. It was shown that the adsorption isotherm coincided with GAB model or Ferro-Fontan model. Moisture absorption process was an exothermic process which was driven by entropy. The effect of moisture on compressibility was evaluated through tensile strength and elastic recovery with water content, pressure force and speed variation. It was supposed that right amount of moisture was required to compression and compaction.

This study was designed to establish the method of characterization of surface free energy(SFE)and evaluate the compaction properties of pharmaceutical materials based on SFE. We investigated the contact angles of materials with water and diiodomethane under different compression pressures. The contact angles of materials at 353 MPa compression pressure were utilized to calculate the related parameters of SFE ultimately. The area under tensile strength-compression pressure curve(AUTSC)and pressure yield(Py)were employed to evaluate the compactibility of material. Additionally, Pearson correlation analysis was utilized to analyze the relationship between the SFE and the compaction properties of pharmaceutical materials. The results exhibited that SFE had a significant correlation with the compaction properties of materials(P < 0.05). Moreover, the related parameters of SFE, i.e., cohesive work(W_co)and polarity index(PI)of SFE, were positively correlated with Py of Heckel equation and negatively related with AUTSC. The higher values of W_co and PI, the stronger repulsive force among the particles, led to a worse compaction behavior. In this study, we established the method for characterization of the compaction behavior of materials based on SFE initially. This study also demonstrated that SFE could evaluate the compaction behavior effectively, which provides a better understanding of compaction behavior for pharmaceutical researchers.

A new type of L. Bulgaricus microcapsule was prepared to improve stability and resistance of L.Bulgaricus probiotics in harsh environments. An optimal method of preparation of L. Bulgaricus microcapsule is as follow. L. Bulgaricus was mixed with 3% alginate solution. The concentration of bacterial suspension was 1×10⁹ cfu·mL^-1. The mixture was microencapsulated by extrusion into 2% CaCl₂ solution with a dispensing equipment. After 30 min solidification, the gel beads were lyophilized to obtain L.Bulgaricus microcapsules. The microencapsulation technology was aimed to improve the stability and survival rate of L. Bulgaricus. The microcapsule was spherical with uniform particle size and intact structure. The tolerance of acid, high temperature, high humidity and the long-term stability of freeze-dried powder and microcapsule were evaluated. The results indicated that microencapsulation technic could greatly improve stability and resistance of L. Bulgaricus probiotics in harsh environments.

In this study, rats were used to evaluate the effect of Radix glycyrrhiza on reducing liver toxicity of Tripterygium wilfordii. Metabonomics techniques were used to analyze the changes of small molecular metabolites and the metabolic pathways involved in the beneficial process. Different groups of rats were given for the extractions from Tripterygium wilfordii and Tripterygium wilfordii together with Radix glycyrrhiza. The general state, pathological changes of liver tissue, biochemical indexes of liver function and the changes of inflammatory factors in rats were observed. The results showed that the liver tissue injury of Tripterygium wilfordii group was significant, and the injury was reduced by Radix glycyrrhiza. Biochemical indexes and inflammatory factors also suggested that Tripterygium wilfordii together with Radix glycyrrhizaeffectively decreased the liver toxicity. HPLC-MS/MS-IT-TOF was used to characterize the difference of serum metabolism in rats. Multivariate statistical analysis was used to screen 15 potential biomarkers, such as fatty acid, glycerol ester, glycerol phosphate, phosphatidylethanolamine and phosphatidylcholine. It mainly involved in 7 metabolic pathways, such as glycerol phospholipid metabolism, linoleic acid metabolism, alpha linoleic acid metabolism, and glycosyl phosphatidylinositol terminal biosynthesis. The results showed that the Tripterygium wilfordii compatibility of Radix glycyrrhizaeffectively decreased the liver toxicity induced by Tripterygium wilfordii. Phospholipid metabolism may be the key metabolic pathway of Tripterygium wilfordii hepatotoxicity and the target of Radix glycyrrhiza. This study provides a reference for the control of liver toxicity of Tripterygium wilfordii.

In this study, the three dimensional(3D)organoid culture system was established by liquid overlay method, and applied as an effective model to evaluate the hepatic injury of susceptible compounds in Polygonum multiflorum Thunb. Compared with the ordinary two dimensional(2D)culture of liver cells, the albumin expression of L02 cells and HepG2 cells were increased by 2.5 and 6.7 times in the 3D organoid culture system, respectively. After the cultivation of 21 days, urea generation levels of 3D culture were increased by 8.3 and 15.5 times. More importantly, HepG2 cells were more suitable to development of organoids than L02 cells. The gene expressions of phase Ⅰ and Ⅱ drug metabolism enzymes of HepG2 cells cultured as 3D organoids were significantly increased than that in 2D culture, such as the fold changes of CYP2C9 was up to 381.9, CYP3A4 to 87.0, CYP2D6 to 312.6. In addition, drug transporter relative genes were also up-regulated. The results demonstrated that the liver synthesis and metabolic function of the 3D model were better than that of the 2D cultured hepatocytes. The results of hepatotoxicity evaluation showed this developed model can be used to assess the hepatotoxicity of acetaminophen and other positive control drugs, which were considered with defined hepatotoxicity. On the 3D culture model, the IC₅₀ value of repeated drug dose administration was significantly lower than that of single dose administration. However, the IC₅₀ of 2, 3, 5, 4'-tetrahydroxy-cis-stilbene-2-O-β-glucoside(cis-SG), which is the susceptible compound in Polygonum multiflorum Thunb., could not be detected in 2D cultured model. With the treatment of a single dose administration in organ 3D culture model, the IC₅₀ of cis-SG was 1.9 times than that of cyclosporine A, and the IC₅₀ of 2, 3, 5, 4'-tetrahydroxy-trans-stilbene-2-O-β-glucoside(trans-SG)was 4.1 times than cis-SG. The hepatotoxicity results of cis-SG and trans-SG on the 3D cultures were similar to in vivo toxicity results obtained in previous work. On organ 3D culture model, the IC₅₀ of cis-SG with repeat of administration decreased compared with that with single dose administration, suggesting that long-term medication may increase the risk of liver injury. In summary, the 3D organoid culture system can be used for a long period to preserve the capacity of liver synthesis and metabolism. The organoids were a model suitable for evaluation of mechanism of the drugs with low toxicity.

This study was designed to investigate the correlation between idiosyncratic liver injury and content of cis-2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside(cis-SG)in radix Polygoni multiflori Preparata(RPMP). In order to compare the effect of hepatotoxicity of different cis-SG contents in RPMP, rats were administered with 50% alcohol extracts of RPMP(7.56 g·kg^-1, via intragastric administration)alone or co-treated with lipopolysaccharide(LPS, 2.8 mg·kg^-1, via tail vein injection). The results showed that no significant alterations of plasma ALT and AST activities were observed in the normal rats. In the LPS treated rats, the group without light treatment and the group with 0.10% cis-SG after light treatment did not exhibit obvious injury in liver. The group with 0.35% cis-SG after light treatment and the group with 0.70% cis-SG after light treatment showed significant increases in ALT, AST, TNF-α, IL-6, NF-κB p65 and apoptosis rate(P < 0.05), causing pathological changes in the liver tissue. Through the content analysis of drug in patients with liver injury, we found that the content of cis-SG( > 0.40%)was generally higher than that of pieces collected from different origins( < 0.10%). The comparative analysis of experiments and clinical data showed that there was a relationship between the content of cis-SG and idiosyncratic liver injury. In order to reduce the risk of clinical medication, the content of cis-SG of 0.10% should be a limit of quality control in the production processing of Polygonum multiflorum.

A series of novel xanthones with terminal amine substituents at xanthone's C3 and C6 positions were designed and synthesized as potential ligands for telomeric G-quadruplex DNA. All the compounds in this series were bound to telomeric G-quadruplex in a "thread intercalation" manner that illustrated both in molecular docking and spectrometric studies. Among them, 10c and 10d showed better binding abilities and specific affinity toward G-quadruplex DNA HTG21 over ctDNA in the fluorescence assay. The antiproliferative activities of four screened compounds were examined in three cancer cells by MTT in vitro, and their inhibitory effects were observed at low micromolar ranges. In addition, the PCR stop assay demonstrated that 10c and 10d effectively inhibited the amplification ability of telomerase.