Naturally sourced amphiphilic peptides as paclitaxel vehicles for breast cancer treatment.

The marketed paclitaxel (PTX) formulation Taxol relies on the application of Cremophor EL as a solubilizer. The major drawback of Taxol is its hypersensitivity reactions and a pretreatment of anti-allergic drugs is a necessity. Therefore, developing an efficient and safe delivery vehicle is a solution to increase PTX treatment outcomes with minimal adverse effects. In this work, we prepared the amphiphilic peptides (termed AmP) from soybean proteins using a facile two-step method. AmP could efficiently solubilize PTX by self-assembling into mixed micelles with D-α-tocopherol polyethylene glycol succinate (TPGS), a common pharmaceutical expedient (PTX@TPGS-AmP). The intravenously administrated PTX@TPGS-AmP exhibited a slow clearance (0.24 mL·(min·kg)-1) and an enhanced AUC (41.4 µg.h/mL), manifesting a 3.6-fold increase compared to Taxol. In a murine 4T1 tumor model, PTX@TPGS-AmP displayed a superior antitumor effect over Taxol. Importantly, safety assessment showed a high biocompatibility of AmP and an i.v. dose up to 2500 mg/kg led to no observable abnormalities in the mice. In summary, the AmP presents a new green and easily-prepared amphiphilic biomaterial, with promising potential as a pharmaceutical excipient for drug delivery.

Synthesis, characterization and corrosion inhibition behavior of 2-aminofluorene bis-Schiff bases in circulating cooling water.

In this work, two new bis-Schiff bases, namely 2-bromoisophthalaldehyde-2-aminofluorene (M1) and glutaraldehyde 2-aminofluorene (M2), were synthesized, and their structures were characterized and confirmed by infrared spectroscopy, Fourier transform mass spectrometry and UV-visible spectroscopy. Their corrosion inhibition performance on carbon steel in simulated circulating cooling water was investigated by weight loss measurements and electrochemical measurements. The potentiodynamic polarization curves confirmed that two bis-Schiff bases are anode-type inhibitors; electrochemical impedance spectroscopy tests showed that M1 and M2 possess the best inhibition efficiencies of 96.25% and 99.15% at the optimal concentration of 2.50 mmol L-1, respectively. The weight loss results showed that M1 and M2 exhibit maximum η w values of 92.62% and 96.31%, respectively. Scanning electron microscopy showed that the inhibitors inhibited carbon steel corrosion. The adsorption isotherm measurements indicated that the two inhibitors exhibited physicochemisorption mechanisms and followed Langmuir adsorption isotherms. The relationships between the molecular structure and inhibition behavior of the inhibitors were explored by density functional theory, frontier molecular orbital studies, and Fukui index analysis, which affirmed that M2 possesses higher corrosion inhibition efficiency than M1.

Synthesis of MOFs/GO composite for corrosion resistance application on carbon steel.

Two unreported metal-organic frameworks [Cu(6-Me-2,3-pydc)(1,10-phen)·7H2O] n (namely Cu-MOF) and [Mn2(2,2'-bca)2(H2O)2] n (namely Mn-MOF) were synthesized by a solvothermal method and their structures were characterized and confirmed by elemental analysis, X-ray single crystal diffraction, Fourier infrared spectroscopy and thermogravimetric analysis. Cu-MOF/graphene (Cu-MOF/GR), Cu-MOF/graphene oxide (Cu-MOF/GO), Mn-MOF/graphene (Mn-MOF/GR) and Mn-MOF/graphene oxide (Mn-MOF/GO) composite materials were successfully synthesized by a solvothermal method and characterized and analyzed by PXRD, SEM and TEM. In order to study the corrosion inhibition properties of the Cu-MOF/GR, Cu-MOF/GO, Mn-MOF/GR and Mn-MOF/GO composite materials on carbon steel, they were mixed with waterborne acrylic varnish to prepare a series of composite coatings to explore in 3.5 wt% NaCl solution by electrochemical measurements and results showed that the total polarization resistance of the 3% Cu-MOF/GO and 3% Mn-MOF/GO composite coatings on the carbon steel surface were relatively large, and were 55 097 and 55 729 Ω cm2, respectively, which could effectively protect the carbon steel from corrosion. After immersion for 30 days, the 3% Mn-MOF/GO composite still maintained high corrosion resistance, the |Z| values were still as high as 23 804 Ω cm2. Therefore, MOFs compounded with GO can produce a synergistic corrosion inhibition effect and improve the corrosion resistance of the coating; this conclusion is well confirmed by the adhesion capability test.

Studies on oral bioavailability and first-pass metabolism of withaferin A in rats using LC-MS/MS and Q-TRAP.

Withaferin A (WA) is one of the major bioactive steroidal lactones with extensive pharmacological activities present in the plant Withania somnifera. The absolute oral bioavailability of WA remains unknown and human-related in vitro data are not available. Therefore, in the present study, the absolute oral bioavailability of WA in male rats and the in vitro screening of absorption factors by Q-trap and LC-MS/MS analysis were conducted to explore possible clinical properties of WA. The developed and validated analytical methods were successfully applied to the pharmacokinetic studies and in vitro measurement of WA. The oral bioavailability was determined to be 32.4 ± 4.8% based on intravenous (5 mg/kg) and oral (10 mg/kg) administrations of WA in male rats. The in vitro results showed that WA could be easily transported across Caco-2 cells and WA did not show as a substrate for P-glycoprotein. Moreover, the stability of WA was similar between male rat and human in simulated gastric fluid (stable), in intestinal microflora solution (slow decrease) and in liver microsomes (rapid depletion, with a half-life of 5.6 min). As such, the first-pass metabolism of WA was further verified by rat intestine-liver in situ perfusion, revealing that WA rapidly decreased and 27.1% remained within 1 h, while the content of three major metabolites (M1, M4, M5) identified by Q-trap increased. This perfusion result is consistent with the oral bioavailability results in vivo. The first-pass metabolism of WA might be the main barrier in achieving good oral bioavailability in male rats and it is predicted to be similar in humans. This study may hold clinical significance.

Effect of Aspergillus flavus Fungal Elicitor on the Production of Terpenoid Indole Alkaloids in Catharanthus roseus Cambial Meristematic Cells.

This study reported the inducing effect of Aspergillus flavus fungal elicitor on biosynthesis of terpenoid indole alkaloids (TIAs) in Catharanthus roseus cambial meristematic cells (CMCs) and its inducing mechanism. According to the results determined by HPLC and HPLC-MS/MS, the optimal condition of the A. flavus elicitor was as follows: after suspension culture of C. roseus CMCs for 6 day, 25 mg/L A. flavus mycelium elicitor were added, and the CMC suspensions were further cultured for another 48 h. In this condition, the contents of vindoline, catharanthine, and ajmaline were 1.45-, 3.29-, and 2.14-times as high as those of the control group, respectively. Transcriptome analysis showed that D4H, G10H, GES, IRS, LAMT, SGD, STR, TDC, and ORCA3 were involved in the regulation of this induction process. The results of qRT-PCR indicated that the increasing accumulations of vindoline, catharanthine, and ajmaline in C. roseus CMCs were correlated with the increasing expression of the above genes. Therefore, A. flavus fungal elicitor could enhance the TIA production of C. roseus CMCs, which might be used as an alternative biotechnological resource for obtaining bioactive alkaloids.

Four New Compounds Obtained from Cultured Cells of Artemisia annua.

Four new compounds obtained from cultured cells of Artemisia annua were reported. Products were detected by HPLC-ELSD/GC-MS and isolated by chromatographic methods. The structures of four new compounds, namely 6-hydroxy arteannuin I (1), 1-hydroxy arteannuin I (2), 2-hydroxy arteannuin J (3), and 14-hydroxy arteannuin J (4), were elucidated using their physico-chemical properties by NMR and MS data analyses. The results from the spontaneous oxidative experiment indicated that the biosynthesis of the new compounds was enzyme-catalyzed. Interestingly, the enzymes in the cultured cells of A. annua showed the abilities of substrate-selective and region-selective hydroxylation of the sesquiterpene lactone. Furthermore, the artemisinin contents were increased by 50% and 80% compared to the control group after the addition of arteannuin I/J to the suspension-cultured cells of A. annua under light and dark culture conditions, respectively.