The effects of pH, surfactant, ion concentration,coformer, and molecular arrangement on the solubility behavior of myricetin cocrystals

Pharmaceutical cocrystals are a promising technology that can be used to improve the solubility of poor aqueous compounds. The objective of this study was to systematically investigate the solubility of myricetin(MYR) cocrystals, including their kinetic solubility, thermodynamic solubility, and intrinsic dissolution rate(IDR). The effects of pH, surfactant, ion concentration, and coformers on the cocrystal solubility were evaluated. Furthermore, single crystal structures of MYR, myricetin–isonicotinamide(MYR–INM) and myricetin–caffeine(MYR–CAF) cocrystals were analyzed to discuss the possible reasons for the enhancement of cocrystal solubility from the perspective of the spatial structure.The results indicated that the kinetic solubility of MYR cocrystals was modulated by pH and cocrystal coformer(CCF) ionization in buffer solution, while it primarily depended on the CCF solubility in pure water. In addition, the solubility of MYR cocrystals was increased in a concentration dependent fashion by the surfactant or ion concentration. The thermodynamic solubility of MYR–INM(1:3) cocrystals decreased with the increases of the pH value of the dissolution media. The IDR of MYR cocrystals was faster than that of MYR in the same medium and extremely fast in pH 4.5 buffer. The improved solubility of MYR cocrystals was probably related to the alternate arrangements of MYR and INM/CAF molecules and increased intermolecular distance. The present study provides some references to investigate the solubility behavior of pharmaceutical cocrystals.

Highly tough and elastic microspheric gel for transarterial catheter embolization in treatment of liver metastasis tumor

Transarterial embolization is a widely recognized clinical treatment method for liver tumors.Given that the soft and easily damaged features of embolic particles may limit tumor embolization efficiency,the present study carries out an attempt of fabricating tough and elastic microspheric gel for promoting embolization efficiency.To promote the toughness of hydrogel,poly(ethylene glycol)-co-poly(ε-caprolactone)-co-poly(ethylene glycol)(PPP)and PPP with two terminal double bonds(PPPDA)are co-assembled into nano-micelles,which are connected with methacrylated chitosan(CSMA)to fabricate microspheric gels via microfluidic technology.Lowering double bond density of micelles promotes the freedom degree of micelles,significantly enhancing hydrogel toughness.To compensate for the strength loss caused by the decrease of double bond density of micelles,phytic acid(PA)are employed to interact with CS to form a physical network,further improving hydrogel strength and toughness.The CS-PPPDA&PPP-PA microspheric gels exhibit higher blocking effect in vitro.A rabbit VX2 liver metastasis tumor model is prepared to verify the embolization efficacy of CS-PPPDA&PPP-PA microspheric gels.Compared with clinical used microspheres,fewer CS-PPPDA&PPP-PA microspheric gels can achieve enough embolization efficiency.After embolization for 14 days,CS-PPPDA&PPP-PA microspheric gels exhibit improved tumor necrosis rate and promoted tumor cells apoptosis with reduced inflammation in surrounding tissues,confirming advanced embolic efficiency of tough microgels.

Analysis of Trace-Level Volatile Compounds in Fresh Turf Crop （Lolium perenne L.） by Gas Chromatography Quadrupole Time-of-Flight Mass Spectrometry

In the traditional research of volatile compounds, some trace-level compounds could not be identified by gas chromatography-mass spectrometry. Target and post-targeted methods were applied in the investigation of trace-level volatile compounds in fresh turf crop （Lolium perenne L.） based on gas chromatography in combination with hybrid quadrupole time-of-flight mass spectrometry. According to literatures published, a target analysis was performed by using retention index, accurate masses of characteristic ions and second-stage mass spectra （MS2 spectra）. And a series of experiments showed that low electron impact energy was beneficial to the improvement of the abundances of low abundance molecular ion peak. peak was beneficial to qualitative analysis. Totally, 60 Enhancing the abundances of low abundance molecular ion volatile compounds were identified, the great majority cornpounds of which were benzeneacetaldehyde （14.8%）, 2,5-dimethyl-pyrazine （9.6%）, and hexanal （9.3%）. Identification was complied by mass spectral search, retention index and accurate masses of characteristic ions.