Preparation of CD123 mono-antibody modified tanshinone ⅡA loaded immunoliposome and its in vitro evaluation / 中国中药杂志

In the study, we developed a novel formulation, CD123 mono-antibody (mAb) modified tanshinone ⅡA loaded immunoliposome (CD123-TanⅡA-ILP) to achieve the targeted drug delivery for leukemia cells. Orthogonal test was used to optimize liposome preparation, and the TanⅡA-loaded PEGylated liposomes (TanⅡA-LP) of S100PC-Chol-(mPEG2000-DSPE)-TanⅡA at 19∶5∶1∶1 molar ratio were prepared by the thin film hydration-probe ultrasonic method. A post-insertion method was applied to prepare CD123-TanⅡA-ILP via thiolated mAb conjugated to the terminal of maleimide-PEG2000-DSPE. The cellular uptake assay was measured by flow cytometry, and the inhibitory effect of CD123-TanⅡA-ILP on NB4 cells proliferation was tested by using MTT assay. The results of cellular uptake assay showed that CD123-ILP could significantly increase the drug uptake of NB4 cells as compared with free drugs and LP. The IC₅₀ values at 48 h incubation were 20.87, 11.71, 7.17 μmol•L⁻¹ respectively for TanⅡA，TanⅡA-LP and CD123-TanⅡA-ILP. CD123-ILP demonstrated a potential and promising targeted drug delivery strategy for acute myelogenous leukemia (AML) treatment.

Preparation and antitumor effects of tanshinone ⅡA loaded albumin nanoparticles / 中国中药杂志

In this study, the tanshinone ⅡA loaded albumin nanoparticles were prepared by high pressure homogenization method. The formulation was optimized by central composite design-response surface method (CCD-RSM), with the particle size, encapsulation efficiency, and drug loading as indexes to investigate their in vitro anti-tumor effect. The results showed that the prepared nanoparticles had uniformly spherical morphology and uniform particle size distribution. The average particle size, encapsulation efficiency and drug loading of nanoparticles were about (175.7± 3.07) nm, 90.8%±1.47% and 5.52%±0.09%, respectively. Tanshinone ⅡA loaded albumin nanoparticles showed a more powerful antitumor effect than free tanshinone ⅡA for human promyelocytic leukemia NB4 cells. The preparation method of the drug-loaded albumin nanoparticles was simple and easy, and can significantly improve the solubility of tanshinone ⅡA, so it was helpful to extend its application in therapies against hematological malignancies.

Quality evaluation and stability investigation of asarone submicro emulsion injection / 中国中药杂志

The content of the asarone submicro emulsion injection was determind by HPLC method, and thereby a quality evaluation method was established based on indexes of pH value, particle size, peroxide value, methoxy aniline values, free fatty acid, lysophosphatidylcholine, visible foreign substances, insoluble particle, sterility, bacterial endotoxin and impurities, etc. The results showed that the injection exhibited uniform physical appearance and all the products were in milkwhite liquid. The content of the three batches products were respectively 102.9%, 100.8%, 97.70% of the labeled amount, with mean particle size of 210-250 nm, and other indexes all met with the standards. The reserved samples showed no obvious change in terms of detection indexes and indicated good stability after the accelerated stability test and long-term stability for 12 months. The quality evaluation method established in this study could be applied to quality control and stability investigation of asarone submicron emulsion injection, which laid a basis for further clinical research and application.

Development of biphasic drug-loading lipid emulsion of Salvia miltiorrhiza and its quality evaluation / 中国中药杂志

The feasibility of simultaneously loading both liposoluble and water-soluble components of Salvia miltiorrhiza in emulsion was discussed, in order to provide new ideas in comprehensive application of effective components in S. miltiorrhiza in terms of technology of pharmaceutics. With tanshinone II (A) and salvianolic acid B as raw materials, soybean phospholipid and poloxamer 188 as emulsifiers, and glycerin as isoosmotic regulator, the central composite design-response surface method was employed to optimize the prescription. The coarse emulsion was prepared with the high-speed shearing method and then homogenized in the high pressure homogenizer. The biphasic drug-loading intravenous emulsion was prepared to investigate its pharmaceutical properties and stability. The prepared emulsion is orange-yellow, with the average diameter of 241 nm and Zeta potential of -35.3 mV. Specifically, the drug loading capacity of tanshinone II (A) and salvianolic acid B were 0.5 g x L(-1) and 1 g x L(-1), respectively, with a good stability among long-term retention samples. According to the results, the prepared emulsion could load liposoluble tanshinone II (A) and water-soluble salvianolic acid B simultaneously, which lays a pharmaceutical foundation for giving full play to the efficacy of S. miltiorrhiza.

Inhibitory effect of tanshinones on proliferation of K562 cell line and its structure-activity relationship / 中国实验血液学杂志

The study was purposed to investigate the growth inhibitory effect of tanshinones on K562 cell line and the relationship between their structures and cytotoxicity. The modified MTT assay was adopted to measure the inhibitory effect of tanshinones at different concentrations and chemical structures on K562 cells, and the changes of cell morphology were observed by inverted phase contrast microscopy. The results indicated that the tanshinones could inhibit the proliferation of K562 cells effectively, and their cytotoxicities on K562 cells showed concentration- and time-dependent manners. The IC(50) of dihydrotanshinone I, tanshinone I, tanshinone IIA and cryptotanshinone at 24 hours were 0.91, 4.04, 5.95, 13.85 µg/ml at 48 hours were 0.37, 1.35, 1.71, 6.71 µg/ml; at 72 hours were 0.33, 0.46, 0.82, 6.02 µg/ml, respectively. It is concluded that all of the four tanshinones have proliferation inhibitory effect on K562 cell line, among them the dihydrotanshinone I is the most active one, followed by tanshinone I, tanshinone IIA and cryptotanshinone subsequently, indicating that the chemical structure of aromatic ring A of tanshinones can enhance their cytotoxicity and the structure of furan ring C may influence the cytotoxicity, but their mechanism is still remained to be further investigated.

Preparation and quality evaluation of intravenous tanshinone II (A) emulsion / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare and evaluate an intravenous emulsion of tanshinone II(A).</p><p><b>METHOD</b>Soybean phospholipid mixing with poloxamer 188 was used as emulsifier. Oleic acid and glycerol were used as co-emulsifier and isoosmotic adjusting agent, respectively. The coarse emulsion was first prepared and following homogenization was carried out for the coarse emulsion by using a high pressure homogenizer.</p><p><b>RESULT</b>The average diameter of the prepared tanshinone II (A) emulsion was 211 nm with a zeta potential of -32. 1 mV. There had no changes of diameter, zeta potential, pH value, content and physical appearance for the tanshinone II (A) emulsion stored at 25 degrees C away from light during one year.</p><p><b>CONCLUSION</b>The physicochemical properties of the prepared tanshinone II (A) emulsion was stable, which could meet the requirements of intravenous administration.</p>

Comparison of kinetic behavior in both plasma and tissue after intravenous administration of alpha-asarone in lipid emulsion and aqueous solution in rats and mice / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the pharmacokinetics and tissue distribution of alpha-asarone in lipid emulsion and aqueous solution for injection and study the feasibility of lipid emulsion of alpha-asarone as the parenteral drug delivery system.</p><p><b>METHOD</b>HPLC was used to determine the drug concentration in rat plasma and mice tissues after intravenous (i.v.) administration of lipid emulsion and aqueous solution of alpha-asarone at a single dose (40 mg x kg(-1)), respectively.</p><p><b>RESULT</b>The plasma concentration-time profiles of lipid emulsion and aqueous solution of alpha-asarone after intravenous administration of them are similar and the drug concentration-time data were fitted to a two-compartment open model. The results of tissues distribution showed that distribution contents of alpha-asarone from lipid emulsion and aqueous solution in vivo are similar in lungs but lipid emulsion increased the uptake in livers and spleens, and decreased the uptake in hearts and kidneys for alpha-asarone.</p><p><b>CONCLUSION</b>The plasma concentration-time profiles of alpha-asarone in lipid emulsion and aqueous solution are similar, but lipid emulsion significantly altered the tissue distribution of alpha-asarone, which may be beneficial to decrease its potential toxicity to heart and kidney.</p>

Studies on characteristics of absorption and separation of traditional Chinese medicine compound prescription by macroporous resin / 中国中药杂志

<p><b>OBJECTIVE</b>Study the characteristics of absorption and separation of traditional Chinese medicine compound prescription using macroporous resin.</p><p><b>METHOD</b>Study the techniquecs and characteristics of absorption and separation of a sample by macroporous resin, which is composed of coptis root, rhubarb and common anemarrhena rhizome, containing alkaloid, anthraquinone and saponin.</p><p><b>RESULT</b>It is proved by qualitative and quantitative researches studies that after absorbed and separated by optimized technics process, most prime effective components or section fractions in traditional Chinese medicine compound prescription can be reserved maintained.</p><p><b>CONCLUSION</b>If the techniquecs of separation is properly designed, the same kind of macropore resin can absorbd and separate various effective components or section in traditional Chinese medicine compound prescription which have with different chemical structures efficiently.</p>

Preparation of liposomes surface-modified with glycyrrhetinic acid targeting to hepatocytes / 中国中药杂志

<p><b>OBJECTIVE</b>To study the preparation of liposomes surface-modified with glycyrrhetinic acid targeting to hepatocytes.</p><p><b>METHOD</b>3-succinic-30-stearyl glycyrrhetinic acid(Suc-GAOSt), one of the amphiphilic glycyrrhetinic acid derivatives, was synthesized as targeting molecules, liposomes surface-modified with glycyrrhetinic acid has been produced with ethanol injection method.</p><p><b>RESULT</b>Targeting molecules can be mixed into the liposomal membrane. It was confirmed that the targeting molecules is 9% of the total lipids at the most in the liposomes.</p><p><b>CONCLUSION</b>Liposomes surface-modified with glycyrrhetinic acid was successfully prepared, which is considered to be a potential approach targeting to hepatocytes.</p>

Preparation of bovine serum albumin nanoparticles surface-modified with glycyrrhizin / 药学学报

<p><b>AIM</b>To study the preparation of bovine serum albumin nanoparticles surface-modified with glycyrrhizin(BSA-NP-GL) targeting to hepatocytes.</p><p><b>METHODS</b>The bovine serum albumin nanoparticles (BSA-NP) were prepared by desolvation process. Glycyrrhizin (GL) was oxidized by sodium periodate to be conjugated to surface reactive amino groups (SRAG) of the BSA-NP. The SRAG were quantified by spectrophotometric method using 2, 4, 6-trinitrobenzenesulfonic acid(TNBS). Glycyrrhetinic acid(GA) hydrolyzed from GL, which was on the surface of BSA-NP-GL was assayed by HPLC after isolation by sephadex G-50. Both methods were used to verify the conjugation achieved. HPLC was used to determine surface density of GL on BSA-NP-GL.</p><p><b>RESULTS</b>The amount of SRAG of the BSA-NP-GL decreased by 19.6% compared with normal BSA-NP. The amount of GL molecule was 9.2% of the total determined SRAG of BSA-NP. The mean diameter of the BSA-NP-GL was 73 nm with round shape. The stability of BSA-NP-GL was constant when it was stored at 25 degrees C and 37 degrees C during 10 days.</p><p><b>CONCLUSION</b>BSA-NP-GL was successfully prepared, which is considered to establish an experimental foundation for further research on its ability for targeting to hepatocytes.</p>

Studies on variation of danshensu content in accelerated stability tests / 中国中药杂志

<p><b>OBJECTIVE</b>To study the variation Laws of content of danshensu accelerated in control and in danshen injection in order to provide reference for stability investigation of danshensu.</p><p><b>METHOD</b>The tests was carried out by classic isothermal method and the content of danshensu was determined by HPLC.</p><p><b>RESULT</b>The contents of danshensu in accelerated tests increase in control and decrease in danshen injection respectively.</p><p><b>CONCLUSION</b>The component of phenic acidity would be hydrolyzed to become danshensu in the accelerated tests. Much attention should be paid to the unusual increase when studies of danshen preparations are carried out.</p>

The study of characteristics of absorption and separation of different glycoside on macropore resins / 中国中药杂志

<p><b>OBJECTIVE</b>To study the absorption and separation of different glycoside on different macropore resins.</p><p><b>METHOD</b>Take baikal skullcap root, cape jasmine fruit and white peony root as samples and study the different characterstics of absorption and separation of these samples on macropore resins such as D101 and so on.</p><p><b>RESULT</b>The static absorption effect of the the three aglycones on six different macropore resins is baicalin > lactiflorin > gardoside. Their elution are 75% CH3OH, 25% CH3OH, and 45% CH3OH. Their elution rates are 60%, 93%, and 93%.</p><p><b>CONCLUSION</b>Similar molecules may not have similar absorption abilities on same macropore resins, but the effect of absorption has something to do with the structures of the molecules, the more double-bonds the molecules have, the greater the absorption force the resins have.</p>