Development of Glycyrrhetinic Acid and Folate Modified Cantharidin Loaded Solid Lipid Nanoparticles for Targeting Hepatocellular Carcinoma

Cantharidin (CTD) is the major component of anticancer drugs obtained from Mylabris Cichorii and has a good inhibitory effect on several cancers, including hepatocellular carcinoma (HCC) and breast cancer. However, due to its toxicity, oral administration can cause various adverse reactions, limiting its clinical application. The aim of this work was to design glycyrrhetinic acid (GA)- and/or folate (FA)-modified solid lipid nanoparticles (SLNs) for the encapsulation of CTD to target HCC. Four CTD-loaded SLNs (cantharidin solid lipid nanoparticles (CSLNs), glycyrrhetinic acid-modified cantharidin solid lipid nanoparticles (GA-CSLNs), folate-modified cantharidin solid lipid nanoparticles (FA-CSLNs), and glycyrrhetinic acid and folate-modified cantharidin solid lipid nanoparticles (GA-FA-CSLNs)) were prepared by the emulsion ultrasonic dispersion method, and their physicochemical parameters were determined (particle size and distribution, morphology, zeta-potential, entrapment efficiency, drug loading, and hemolysis). Additionally, the antitumor activities of the four SLNs were evaluated comprehensively by tests for cytotoxicity, cell migration, cell cycle, apoptosis, cellular uptake, competition suppression assay, and in vivo tumor suppression assay. Four SLNs showed spherical shapes and mean diameters in the range of 75–110 nm with size dispersion (PDI) within the range of 0.19–0.50 and zeta-potential approximately –10 mV. The entrapment efficiency of CTD in SLNs was higher than 95% for all tested formulations, and no hemolysis was observed. Compared to GA-CSLNs or CSLNs, GA-FA-CSLNs and FA-CSLNs showed stronger cytotoxicity on hepatocellular carcinoma cells (HepG2), and the cytotoxicity of GA-FA-CSLNs on hepatocyte cells (L-02) was remarkably reduced compared with other formulations. GA-FA-CSLNs and FA-CSLNs also increased the inhibition of HepG2 cell migration, and FA-CSLNs had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells were arrested mainly in the S phase and G2/M phase. Analysis of competition inhibition experiments showed that GA and FA ligands had targeted effects on HepG2 cells. The in vivo tumor inhibition experiment showed that GA-FA-CSLNs and FA-CSLNs had excellent tumor inhibition ability—their tumor inhibition rates were 96.46% and 89.92%, respectively. Our results indicate that GA-FA-CSLNs and FA-CSLNs have a promising future in the therapeutic intervention of HCC.     

Optimization of the Conditions of Solid Lipid Nanoparticles (SLN) Synthesis

Solid lipid nanoparticles (SLNs) have been synthesized as potential drug delivery systems. They are classified as solid lipid nanocarriers that can successfully carry both hydrophilic and hydrophobic drugs. SLNs are based on a biocompatible lipid matrix that is enzymatically degraded into natural components found in the human body. Solid lipid nanoparticles are suitable for the incorporation of hydrophobic active ingredients such as curcumin. The study included the optimization of lipid nanoparticle composition, incorporation of the active compound (curcumin), a stability evaluation of the obtained nanocarriers and characterization of their lipid matrix. Through process optimization, a dispersion of solid lipid nanoparticles (solid lipid:surfactant—2:1.25 weight ratio) predisposed to the incorporation of curcumin was developed. The encapsulation efficiency of the active ingredient was determined to be 99.80%. In stability studies, it was found that the most suitable conditions for conducting high-pressure homogenization are 300 bar pressure, three cycles and a closed-loop system. This yields the required values of the physicochemical parameters (a particle size within a 200–450 nm range; a polydispersity index of <30%; and a zeta potential of about |±30 mV|). In this work, closed-loop high-pressure homogenization was used for the first time and compared to the currently preferred open-loop method.     

2-(2-喹啉偶氮)-5-二乙氨基苯甲酸固相萃取光度法测定环境水样中的镍

用2－（2－喹啉偶氮）－5－二乙氨基苯甲酸（QADEAB）与镍的显色反应及Waters Porapak^R Sep-Park固术萃取小柱对显色络合物的固相萃取，建立了测定水样中μg/L级镍的新方法。水样中的镍在pH=8.0的硼酸－磷酸二氢钾缓冲介质中和Tween 80存在下与QADEAB反应生成2：1稳定有色络合物，该络合物可用Waters Porapak^R Sep-Park固相萃取小柱富集，用乙醇洗脱后用光度法测定，可测定水样中μg/L级的镍。方法用于几种环境水样分析，结果令人满意。     

Preparation of Co-Processed Excipients for Controlled-Release of Drugs Assembled with Solid Lipid Nanoparticles and Direct Compression Materials

The purpose of the study was to develop a novel, directly compressible, co-processed excipient capable of providing a controlled-release drug system for the pharmaceutical industry. A co-processed powder was formed by adsorption of solid lipid nanoparticles (SLN) as a controlled-release film onto a functional excipient, in this case, dicalcium phosphate dihydrate (DPD), for direct compression (Di-Tab^®). The co-processed excipient has advantages: easy to implement; solvent-free; industrial scaling-up; good rheological and compressibility properties; and the capability to form an inert platform. Six different batches of Di-Tab^®:SLN weight ratios were prepared (4:0.6, 3:0.6, 2:0.6, 1:0.6, 0.5:0.6, and 0.25:0.6). BCS class III ranitidine hydrochloride was selected as a drug model to evaluate the mixture’s controlled-release capabilities. The co-processed excipients were characterized in terms of powder rheology and dissolution rate. The best Di-Tab^®:SLN ratio proved to be 2:0.6, as it showed high functionality with good flow and compressibility properties (Carr Index = 16 ± 1, Hausner Index = 1.19 ± 0.04). This ratio could control release for up to 8 h, so it fits the ideal profile calculated based on biopharmaceutical data. The compressed systems obtained using this powder mixture behave as a matrix platform in which Fickian diffusion governs the release. The Higuchi model can explain their behavior.     

铈（Ⅲ）,铈（Ⅳ）与植酸生成的固态配合物的研究

铈（Ⅲ）、铈（Ⅳ）与植酸生成的固态配合物的研究黎晓霞杨瑛＊刘建民杨汝栋（兰州大学化学系兰州７３００００）关键词铈（Ⅲ），铈（Ⅳ），植酸，固态配合物１９９６－１１－２０收稿，１９９７－０５－２６修回植酸（Ｈ１２ＩＨＰ）作为沉淀剂已被用于Ｔｈ４＋的定量测...     

固体超强酸SO_4~(2-)/SiO_2-TiO_2催化合成异维生素C钠

在异维生素C钠(D-VcNa)的合成过程中,以SO42-/S iO2-TiO2复合固体超强酸作为酯化反应催化剂,2-酮基-D-葡萄糖酸(2-KGA)和甲醇为原料,采用精馏脱水酯化工艺,不断除去酯化过程中产生的水。催化剂的最佳焙烧温度为550℃,催化剂用量为2.5%;反应时间3~4 h,产品收率为88.6%,催化剂的重复使用性较好,催化体系优于硫酸法。     

固体酸SO_4~(2-)/ZrO_2-MoO_3催化合成富马酸二甲酯

在固体酸SO2-4/ZrO2 MoO3催化下,由马来酸酐和甲醇催化合成了富马酸二甲酯.探讨了催化剂用量,原料配比,反应时间对产率的影响.最佳反应条件为:醇酸摩尔比为6∶1,反应时间3h,催化剂占反应物总质量的1.5%,产物收率在93%以上.     

固体酸ZrO2-Ce2O3／SO4^2-催化合成丙二酸二丁酯

以含铈固体超强酸ZrO2-Ce2O3／SO4^2-为催化剂，丙二酸和正丁醇为原料合成了丙二酸二丁酯。最佳反应条件为：催化剂活化温度500℃，丙二酸100mmol，n(酸)：n(醇)=1．0：2．5，催化剂用量1g,反应时间2h，酯化率达95．8％。结果表明，加入铈有助于提高固体超强酸的使用寿命。     

Thermodynamic Evaluation of the Interactions between Anticancer Pt(II) Complexes and Model Proteins

In this work, we have analysed the binding of the Pt(II) complexes ([PtCl(4′-phenyl-2,2′:6′,2″-terpyridine)](CF₃SO₃) (1), [PtI(4′-phenyl-2,2′:6′,2″-terpyridine)](CF₃SO₃) (2) and [PtCl(1,3-di(2-pyridyl)benzene) (3)] with selected model proteins (hen egg-white lysozyme, HEWL, and ribonuclease A, RNase A). Platinum coordination compounds are intensively studied to develop improved anticancer agents. In this regard, a critical issue is the possible role of Pt-protein interactions in their mechanisms of action. Multiple techniques such as differential scanning calorimetry (DSC), electrospray ionization mass spectrometry (ESI-MS) and UV-Vis absorbance titrations were used to enlighten the details of the binding to the different biosubstrates. On the one hand, it may be concluded that the affinity of 3 for the proteins is low. On the other hand, 1 and 2 strongly bind them, but with major binding mode differences when switching from HEWL to RNase A. Both 1 and 2 bind to HEWL with a non-specific (DSC) and non-covalent (ESI-MS) binding mode, dominated by a 1:1 binding stoichiometry (UV-Vis). ESI-MS data indicate a protein-driven chloride loss that does not convert into a covalent bond, likely due to the unfavourable complexes’ geometries and steric hindrance. This result, together with the significant changes of the absorbance profiles of the complex upon interaction, suggest an electrostatic binding mode supported by some stacking interaction of the aromatic ligand. Very differently, in the case of RNase A, slow formation of covalent adducts occurs (DSC, ESI-MS). The reactivity is higher for the iodo-compound 2, in agreement with iodine lability higher than chlorine.     

Titration Calorimetric Investigation of Interactions of Zinc(II), Nickel(II), and Copper(II) Tetraphenylporphine Complexes with Pyridine in Three Solvents

Titration calorimetry was used in a thermodynamic study on the interactions of pyridine (Py) with zinc(II)-tetraphenylporphine (ZnTPP), nickel(II)-tetraphenyl-porphine (NiTPP), and copper(II)-tetraphenylporphine (CuTPP) in benzene, chloroform, and carbon tetrachloride solutions. The coordinating properties of the metalloporphyrins in relation to pyridine were found to diminish in the order ZnTPP > CuTPP > NiTPP. Solvation effects were estimated from the interactions between metalloporphyrins (MP) and Py. The more negative values of the enthalpy and entropy of reaction of ZnTPP with Py, following the order of solvents CCl₄ > C₆H₆ > CHCl₃, was found to be related to the different types of (MP–solvent) and (Py–solvent) interactions. The NiTPP and CuTPP complexes showed the opposite trend.     

磁性超细固体酸催化剂SO4^2——ZrO2／Fe3O4的组装及表征

将磁性Fe3O4纳米材料和SO4^2--ZrO2固体酸进行组装，制得一系列具有磁性和超细粒子结构的固体酸催化剂SO4^2--ZrO2/Fe3O4，采用XRD，TG－DTA和XPS等分析测试手段对催化剂的结构和性能进行了表征。并分析和测试了催化剂的磁学性能、比表面积、粒度分布和元素的组成等物理化学性质。该催化剂具有较小的粒度、较高的磁性及酯化催化活性，对乙酸丁酯合成反应的催化活性可达66％；利用Fe3O4的磁性可对催化剂进行分离和回收。经高温处理后，固体超强酸的形成对催化剂磁性、比表面积、表相原子的电子结合能以及各组分形态均有显著影响。     

Titration Calorimetric Investigations on the Interactions of Zn(II) Porphyrin Complexes with Pyridine in Benzene and Chloroform at 298.15 K

Titration calorimetry was used in a thermodynamic study on the interactions of pyridine with natural zinc(II) porphyrin derivatives in benzene and chloroform at 298.15 K. The ability of zinc porphyrins to coordinate to pyridine is higher in benzene than in chloroform and also depends on the molecular structure of the metalloporphyrin.This revised version was published online in November 2005 with corrections to the Cover Date.     

新型疏水性固体酸Zr(SO4)2/AC催化剂的制备及其催化性能

 将Zr(SO4)2(CZ)负载在活性炭(AC)上制备疏水性固体酸CZ/AC催化剂,用于丙烯酸与正辛醇的酯化反应,考察了催化剂制备条件对催化剂活性和疏水性的影响. 结果表明,以60～80目的活性炭负载30%的Zr(SO4)2并于110 ℃干燥后制得的CZ/AC催化剂的活性最高,丙烯酸转化率可达100.0%; CZ/AC催化剂循环使用3次,丙烯酸的转化率仍保持在97.5%. 采用X射线衍射(XRD)、傅里叶变换红外光谱(FT-IR)、X射线光电子能谱(XPS)和低温N2吸附方法对催化剂的结构和酸性进行了表征, XRD及XPS测试结果均表明硫酸锆以非晶态形式高度分散在活性炭的表面; 原位红外吸附NH3测试中在 1521 和 1695 cm-1处有两个吸收峰,表明催化剂表面存在L酸和B酸. 负载型疏水性固体酸CZ/AC催化剂的酸强度、酸量、催化活性和疏水性能均高于Zr(SO4)2.     

Heat Capacities and Thermodynamic Properties of 3-（2,2-Dichloroethenyl）-2,2-dimethylcyclopropanecarboxylic Acid

The heat capacities of 3 - (2,2-dichloroethenyl) -2,2-dimethylcyclopropanecarboxylic acid ( a racemic mixture,molar ratio of cis-/trans-structure is 35/65) in a temperature range from 78 to 389 K were measured with a precise automatic adiabatic calorimeter. The sample was prepared with a purity of 98.75% ( molar fraction). A solid-liquid fusion phase transition was observed in the experimental temperature range. The melting point, Tm, enthalpy and entropy of fusion, △fusHm, △fusSm, of the acid were determined to be ( 331.48 ± 0.03 ) K, ( 16. 321 ± 0.031 ) kJ/mol,and (49.24 ± 0.19) J/( K·mol), respectively. The thermodynamic functions of the sample, HT - H298.15, ST -S298.15 and GT - G298.15, were reported at a temperature intervals of 5 K. The thermal decomposition of the sample was studied using thermogravimetric (TG) analytic technique, the thermal decomposition starts at ca. 418 K and ends at ca. 544 K, the maximum decomposition rate was obtained at 510 K. The order of reaction, preexponential factor and activation energy are n =0.23, A =7. 3 × 107 min -1, E =70.64 KJ/mol, respectively.     

过渡金属离子掺杂CeO_2-SO_4~(2-)固体酸的结构、redox性能、吸附性能及NH_3-SCR活性研究

通过溶胶凝胶法制备了Cux+,Fex+,Nix+和Zrx+掺杂的CeO2-SO42-固体酸NH3-SCR催化剂。利用XRD,IR,NH3-TPD,NH3-TPO,NOx-TPD和NO-TPO等手段研究了过渡金属离子掺杂对CeO2-SO42-催化剂结构、吸附性能、redox性能和NH3-SCR活性的影响。试验结果表明,Nix+和Zrx+掺杂的CeO2-SO42-固体酸催化剂的NH3-SCR活性最好,在250～360℃温度范围内NOx的转化率可达80%以上;Cux+掺杂催化剂的NOx和NH3吸附性能较差,导致催化剂的脱硝效率较低,而Fex+掺杂催化剂虽然具有较好的NH3和NOx吸附性能,但该催化剂对NH3的氧化性能较高,导致高温条件下还原剂的氧化,从而降低了CeO2-SO42-催化剂的活性;Nix+和Zrx+掺杂可以在提高催化剂吸附性能的基础上保持较低的NH3氧化活性,从而使CeO2-SO24-催化剂保持较高的脱硝性能。     

微波水热改性制备S_2O_8~(2-)/Fe_2O_3-SiO_2固体酸及催化性能

对共沉淀法得到的Fe2O3-SiO2混合氧化物前驱物进行微波水热改性处理,经浸渍(NH4)2S2O8后再焙烧得S2O82-/Fe2O3-SiO2固体酸催化剂。用XRD、TEM、N2气吸附/脱附及化学分析方法对其进行了表征,用乙酸/丁醇酯化催化反应评估固体酸的催化性能,并与通常条件下制得的催化剂进行了比较。结果显示,引入SiO2会延迟Fe2O3晶体的形成与长大;对前驱物用250W的微波水热改性处理1.5h,制得的固体酸具有适中的比表面积、均匀的孔径分布,含硫量为6.02%,比表面积为37.1m2/g。该固体酸对乙酸丁醇酯化反应有很高的催化活性,催化酯化反应3h,乙酸的转化率高达97.7%。     

SO4^2—／ZrO2的相结构和超强酸性及其对丁烷异构化反应的催化活性

通过沉淀、回流和掺杂等方法制备了ZrO2呈四方相及单斜相的SO4^2-／ZrO2（SZ），并用XRD，TEM，低温N2－BET和吡啶吸附IR等技术定量测量地测定和探讨了SZ的结构特征和表面超强酸性及其对丁烷异构化反应的催化活性，结果表明，ZrO2呈单斜相结构的SZ表面Broensted（B）酸与Lewis（L）酸的浓度比[B]/[L]较ZrO2以四方相为主的SZ高约40％，但其对丁烷异构化反应的比催化活性则较后者低约31％，由掺Mg^2 所制备的ZrO2呈四方相的SMZ具有与ZrO2呈纯单斜相的SZ非常接近的[B]/[L]比，且表现出比末掺Mg^2 的ZrO2以四方相为主的SZ更高的比催化活性，从催化剂晶结构对表面B酸浓度及强度影响的角度进行了讨论。     

GaxCs2.5-3xH0.5PW12O40的固相法制备及其催化正丁烷异构化反应的活性

利用室温固相法制备了一系列掺镓的钨磷酸铯盐催化剂GaxCs2.5-3xH0.5PW12O40(x=0.05,0.1,0.15).与钨磷酸铯盐相比,掺镓的钨磷酸铯盐催化剂的结构未产生变化,但其酸强度提高,在正丁烷异构化反应中催化活性增强,其中以Ga0.1Cs2.2H0.5PW12O40和Ga0.15Cs2.05H0.5P...     

钒改性对SO4^2-/ZrO2-Al2O3固体酸催化剂结构与催化性能的影响

采用共沉淀法和浸渍法在不同条件下制备了V2O5-SO42-/ZrO2-Al2O3系列固体超强酸催化剂.使用乙酸与正丁醇酯化反应评价了催化剂活性,并通过热重、X射线衍射、红外光谱、比表面积测定和X射线光电子能谱等表征方法考察了催化剂结构和性能的关系.结果表明,载体在0℃陈化,最终样品于600℃焙烧,钒浸渍浓度为0.005 mol/L,且后于硫酸溶液浸渍时制得的催化剂活性最高,酯化率为99.71%,且具有较好的重复使用性.V的引入使活性四方相ZrO2更加稳定,0℃陈化促进了四方相ZrO2微晶生成,600℃焙烧使催化剂既具有较多活性四方相ZrO2,又具有较大比表面积,从而提高了催化剂活性.催化剂中形成了固体超强酸结构,且改性后S=O吸收峰及劈裂程度增强,催化剂活性中心数目增加,Al2O3,ZrO2,SO42-和助剂V发生了相互作用.低温陈化虽然提高了催化剂的活性,但是略微降低了催化剂的热稳定性.