•The TBO hydrogel formulation was optimized by response surface methodology.•Photodynamic therapy with optimal TBO hydrogel showed strong antimicrobial activity.•The optimal TBO hydrogel was stable over time about appearance, pH and viscosity.Photodynamic therapy with toluidine blue O (TBO) hydrogel exhibits antibacterial activity against Staphylococcus aureus and Escherichia coli in this paper. The response surface methodology is employed to optimize formulations for antibacterial activity. The optimal formulations are carbomer concentration of 3% (w/v), TBO concentration of 0.1 mg/mL and the quality ratio of NaOH and carbomer of 0.4 (w/w). Under the optimized formulations, the log-transformed of CFU mL− 1 on the Staphylococcus aureus and Escherichia coli are 0.84 and 1.26 (the log-transformed of CFU mL− 1 of negative control groups on the Staphylococcus aureus and Escherichia coli are 8.21 and 8.47), respectively. In comparison with photodynamic therapy with TBO aqueous solution, the proposed formulations provide a much stronger antibacterial activity against Staphylococcus aureus and Escherichia coli. TBO hydrogels are stable during 6 weeks at three different temperatures (4, 25 and 40 °C) with respect to no change of color, transparency, pH and viscosity. 50% and 68.26% of TBO are released from carbomer hydrogel after 4 h and 24 h, respectively. TBO hydrogel alone or light alone (630 nm) treatment is incapable of showing antibacterial activity against Staphylococcus aureus and Escherichia coli. Therefore, photodynamic therapy with the novel optimized TBO hydrogel formulations is a promising treatment strategy for periodontitis.Download high-res image (229KB)Download full-size image

•Extraction conditions were optimized by response surface methodology.•The model for optimization was precise and reliable.•The optimum conditions differed according to yield or antioxidant value.•IL-based MAE is a highly efficient and fast method.Ionic liquid-based microwave-assisted extraction was successfully applied for extracting curcuminoids from Curcuma longa L., and the antioxidant value of the extract was determined by DPPH and TRAP methods Response surface methodology was used to optimize experimental conditions for extraction yield and antioxidant value. The results indicated that the optimal extraction solvent was 0.3 mol/L 1-octyl-3-methylimidazolium bromide. Considering extraction yield as the reference index, the optimum conditions were as follows: extraction temperature 55 °C, extraction time 8 min, and solid-liquid ratio 0.5/30 (g/mL). Considering antioxidant value as reference index, the optimum conditions were as follows: extraction temperature 70 °C, extraction time 2 min, and solid-liquid ratio 0.5/30 (g/mL). Under optimum conditions (extraction yield as reference index), the average yield of three kinds of curcuminoids was 1.77%. Compared with ultrasound-assisted extraction, microwave-assisted extraction is a highly efficient and pollution-free method, which requires a shorter extraction time and less energy consumption.Download high-res image (153KB)Download full-size image

•Development of a UPLC–MS/MS method for berberine and its derivatives in rat plasma.•Its derivative B4 has increased Cmax (8-fold), t1/2 (2-fold), and AUC than berberine.•Inversely, its derivative A4 has decreased Cmax, t1/2, and AUC than berberine, suggesting a tight structure-activity relationship of these compounds.•Oral bioavailability of A4,B4, and berberine was 0.12%, 3.4% and 0.7%, respectively.•Organ accumulation of B4 was intestine > liver > heart > kidney > lung > spleen > plasma, proving a deeply targeting property of B4.An ultra-performance liquid chromatography with tandem mass spectrometric detection method was developed for the detection of berberine and its derivatives (A4, B4) in rat plasma and other organs. This validated method was successfully applied to our pharmacokinetic study of BBR derivatives in rats. At the same dose of administration, the Cmax of B4 was about eight times higher than BBR, and its half-life was approximately two times longer than BBR, according to the bigger areas under plasma concentration curves. Inversely, the pharmacokinetic parameter levels of A4 were all inferior to BBR, suggesting a tight structure-activity relationship of these compounds. Small dose of parenteral administration was used for the study of absolute oral bioavailability of A4, B4, and BBR, and the results calculated were 0.12%, 3.4% and 0.7%, respectively. The accumulations of B4 among all organs were intestine > liver > heart > kidney > lung > spleen > plasma, proving a deeply targeting property of B4, which met our experimental assumption. Together, the experimental results proved that compared with BBR and A4, the derivative B4 had higher absolute oral bioavailability and the ability of deeply targeting so that can be likely used in some organ-targeted diseases.

The goal of this work is to develop the method of preparing folate (FA)-decorated human serum albumin (HSA) loaded with nano-hydroxycamptothecin (nHCPT) nanoparticles (NPs) (FA-HSA-nHCPT-NPs) and to explore its antitumor activity in vivo and in vitro. FA-HSA-nHCPT-NPs were obtained by preparing nHCPT by a high-pressure homogenization technique followed with an anti-solvent method. The drug-loading efficiency of the FA-HSA-nHCPT-NPs was 7.8%. We adopted the human breast cancer cells (FA receptor-expressing MCF-7 cells) and BALB/c mice inoculated with human MCF-7 cells to determine the antitumor activity of FA-HSA-nHCPT-NPs in vitro and in vivo, respectively. The antitumor activity of FA-HSA-nHCPT-NPs was stronger than that of the raw HCPT in both conditions. Tissue distribution analysis showed that the FA-HSA-nHCPT-NPs carried more HCPT to tumors than the raw HCPT. The tumor inhibitory rate of FA-HSA-nHCPT-NPs was much higher compared with the raw HCPT. Th7us, the FA-HSA-nHCPT-NPs could serve as a viable delivery system with an obvious target effect on tumor.