[Distribution of surface components in spray-dried powder of binary system of berberine hydrochloride and dextran based on hydrodynamic size].

The present study explored the correlation between the hydrodynamic size(i.e., hydrated particle size) and the surface component distribution of spray-dried powder based on the binary system model of berberine hydrochloride and dextran. A variety of mixture solutions containing substances of different proportions were prepared, and the hydrated particle sizes of the solutions were measured by laser light scattering technique. Then the effects of molecular weight and mixing proportion on the particle size were analyzed. After the solutions were spray-dried, the surface components of spray-dried powder were determined by X-ray photoelectron spectroscopy. The changes of hydrated particle size of the two substances in different solutions were measured with the altered solution environments, and the distribution of surface components after spray-drying was observed. The results of particle size measurement showed that different solution environments would change the hydrodynamic size of substances. Specifically, the particle size of berberine hydrochloride increased with the increase in ionic strength and solution pH, while the particle size of dextran decreased with the increase in ionic strength and increased with the increase in solution pH. The results of surface components of the spray-dried powder indicated that berberine hydrochloride was prone to accumulate on the surface of particles during spray-drying because of its large hydrodynamic size. Therefore, hydrodynamic size is considered an important factor affecting the surface component distribution of spray-dried powder. As revealed by scanning electron microscopy of the particle morphology of spray-dried powder, the particles of berberine hydrochloride spray-dried powder were irregularly elliptic, and the particles of dextran and mixture spray-dried powders were irregularly spherical with the shrunken surface. Finally, the FT4 powder rheometer and DVS instrument were used to determine the stability, adhesion, and hygroscopicity of the powder. The results showed that when berberine hydrochloride was enriched on the surface, the adhesion of the mixture increased and the fluidity became worse, but the hygroscopicity was improved to a certain extent. In addition, as found by hygroscopic kinetic curve fitting of spray-dried powder, the hygroscopic behaviors of all spray-dried powder conformed to the double exponential function.

Cholesterol Microdomain Enhances the Biofilm Eradication of Antibiotic Liposomes.

Resistance and tolerance of biofilms to antibiotics is the greatest challenge in the treatment of bacterial infections. Therefore, developing an effective strategy against biofilms is a top priority. Liposomes are widely used as antibiotic drug carriers; however, common liposomes lack affinity for biofilms. Herein, biofilm-targeted antibiotic liposomes are created by simply adjusting their cholesterol content. The tailored liposomes exhibit significantly enhanced bacterial inhibition and biofilm eradication effects that are positively correlated with the cholesterol content of liposomes. The experiments further demonstrate that this enhanced effect can be ascribed to the effective drug release through the pores, which are formed by the combination of cholesterol microdomains in liposomal lipid bilayers with membrane-damaged toxins in biofilms. Consequently, liposome encapsulation with a high cholesterol concentration improves noticeably the pharmacodynamics and biocompatibility of antibiotics after pulmonary administration. This work may provide a new direction for the development of antibiofilm formulations that can be widely used for the treatment of infections caused by bacterial biofilms.

Inhibition of Lysozyme Amyloid Fibrillation by Silybin Diastereoisomers: The Effects of Stereochemistry.

Silybin is a flavonoid lignin compound consisting of two diastereomers with nearly equal molar ratios. It has been reported that silybin can effectively inhibit the aggregation of amyloid protein, but the difference between the two silybin diastereomers has been rarely studied. In this work, the inhibitory ability of silybin to hen egg-white lysozyme (HEWL) was demonstrated, and the difference of kinetic parameters of two diastereomers was analyzed. Fluorescence quenching titration was utilized to analyze the binding differences to native HEWL between the diastereomers, and transmission electron microscopy (TEM) was utilized to analyze the characteristics of the surface of various samples. The differences between hydrophobicity and the secondary structure among several HEWL samples were measured by the 8-anilino-1-naphthalene sulfonic (ANS) acid fluorescence probe, Raman spectra, and far-UV circular dichroism. Moreover, the differences in the binding energy of these two diastereomers with HEWL were analyzed by molecular docking. Also, we have investigated the effect of silybin diastereomers on HEWL fibril-induced cytotoxicity in SH-SY5Y cells. Results show that silybin has a certain inhibitory effect on the HEWL fibrillogenesis process, while silybin B (SB) has a more significant inhibitory effect than silybin A (SA), especially at high concentrations. This work provides some insights into the screening of amyloid inhibitors from complicated natural products and indicates that SB has the prospect of further development as an amyloid inhibitor.

Inhalation of Tetrandrine-hydroxypropyl-ß-cyclodextrin Inclusion Complexes for Pulmonary Fibrosis Treatment.

Pulmonary fibrosis (PF) is a kind of interstitial lung disease with the features of progressive and often fatal dyspnea. Tetrandrine (TET) is the major active constituent of Chinese herbal Stephania tetrandra S. Moore, which has already applied clinically to treat rheumatism, lung cancer, and silicosis. In this work, a tetrandrine-hydroxypropyl-ß-cyclodextrin inclusion compound (TET-HP-ß-CD) was developed for the treatment of pulmonary fibrosis via inhalation administration. TET-HP-ß-CD was prepared by the freeze-drying method and identified using the cascade impactor, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectrum (FT-IR). A bleomycin-induced pulmonary fibrosis rat model was used to assess the effects of inhaled TET and TET-HP-ß-CD. Animal survival, hydroxyproline content in the lungs, and lung histology were detected. The results showed that inhalation of TET-HP-ß-CD alleviated inflammation and fibrosis, limited the accumulation of hydroxyproline in the lungs, regulated protein expression in PF development, and improved postoperative survival. Moreover, nebulized delivery of TET-HP-ß-CD accumulated chiefly in the lungs and limited systemic distribution compared with intravenous administration. The present results indicated that inhalation of TET-HP-ß-CD is an attractive candidate for the treatment of pulmonary fibrosis.

Specificity of Pseudomonas isolates on healthy and Fusarium head blight-infected spikelets of wheat heads.

The specificity of culturable bacteria on healthy and Fusarium head blight (FHB)-infected spikelets of wheat heads was investigated to find a candidate of biocontrol agents against FHB. The bacterial genus Pseudomonas was commonly isolated from the tissues, and phylogenetic analysis using 16S ribosomal RNA gene sequences of isolates of the genera revealed that particular phylogenetic groups in the genus specifically inhabited either healthy or infected spikelet tissues. The specificity of each group was suggested to be due to differences in the ability to form biofilms and colonize spikelet tissues; isolates originated from healthy spikelets formed biofilms on polyvinyl chloride microplate wells and highly colonized the spikelet tissues. Other bacterial groups obtained from FHB-infected spikelets less formed biofilms and attached with low densities on the spikelet tissues. Their colonization on the tissues, however, was promoted when co-inoculated with the causal pathogenic fungus, Fusarium graminearum, and several isolates were observed to smash the mycelia in vivo. Moreover, based on results of in vitro mycelial growth inhibition activity, the diseased tissue-originated isolates were verified to have a negative effect on the fungal growth. These results suggest that Pseudomonas isolates obtained from infected spikelet tissues were highly associated with the FHB pathogen and have potential as candidates for biological control against FHB.