Development of eugenol-loaded submicron emulsion and its antiepileptic effect through regulating the oxidative stress.

The purpose of this study was to develop an injectable submicron emulsion of eugenol (Eug-SE) and to investigate its antagonism on epilepsy. The formulation was optimized using a complete randomized design, comprising 5% (w/v) eugenol, 5% (w/v) soybean oil, 1.2% (w/v) egg phosphatidylcholine, 0.

Enhancing cytotoxicity of daunorubicin on drug-resistant leukaemia cells with microparticle-mediated drug delivery system.

Multidrug resistance is considered as a major obstacle for effective tumour chemotherapy. With the ability to deliver drugs into tumour cells, microparticles may act as a drug delivery vehicle to overcome drug resistance. In the present study, we developed an approach employing daunorubicin-loaded microparticles to surmount the drug resistance in leukaemia.

[Preparation and antitumor effects of tanshinone ⅡA loaded albumin nanoparticles].

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.

[Preparation of CD123 mono-antibody modified tanshinone ⅡA loaded immunoliposome and its in vitro evaluation].

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.

Anti-CD123 antibody-modified niosomes for targeted delivery of daunorubicin against acute myeloid leukemia.

A novel niosomal delivery system was designed and investigated for the targeted delivery of daunorubicin (DNR) against acute myeloid leukemia (AML). Anti-CD123 antibodies conjugated to Mal-PEG-DSPE were incorporated into normal niosomes (NS) via a post insertion method to afford antibody-modified niosomes (CD123-NS). Next, NS was modified with varying densities of antibody (0.

Total Synthesis of Tanshinone I.

A novel total synthesis of tanshinone I (1) via the intermediate 3-hydroxy-8-methyl-1,4-phenanthrenedione (8) is described. The low overall yields and the use of expensive reagents in the synthesis process were minimized by the use of the Diels-Alder reaction to directly construct the 1,4-phenanthrenedione scaffold, providing tanshinone I (1) in only three steps.

[Quality evaluation and stability investigation of asarone submicro emulsion injection].

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.

[Development of biphasic drug-loading lipid emulsion of Salvia miltiorrhiza and its quality evaluation].

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.

Development of synthetic peptide-modified liposomes with LDL receptor targeting capacity and improved anticancer activity.

In this study, we report an active targeting liposomal formulation directed by a novel peptide (AA13) that specifically binds to the low density lipoprotein receptor (LDLR) overexpressed on acute myeloid leukemia (AML) cells. The objectives of this study were to evaluate the in vitro and in vivo tumor drug targeting delivery of AA13-anchored liposomes on AML cells. AA13 conjugated to the distal end of DSPE-PEG2000-maleimide was incorporated into the liposomes via a postinsertion method.

Development of intravenous lipid emulsion of α-asarone with significantly improved safety and enhanced efficacy.

Severe adverse events have been frequently associated with taking the commercially available formulation of α-asarone injection (α-asarone-I). Hence, we sought to develop an intravenous lipid emulsion of α-asarone (α-asarone-LE), where we hypothesized that these adverse events could be prevented. Using a central composite design-response surface methodology, we developed and optimized an emulsion formulation of α-asarone-LE that composed of 10.

Development of 2-hydroxymethyl-3,5,6-trimethylpyrazine palmitate-loaded lipid emulsion: formulation, optimization, characterization, pharmacokinetics, biodistribution and pharmacodynamics.

Background: Tetramethylpyrazine (TMP) is used to treat cerebrovascular and cardiovascular diseases. However, it displays a short half-life that restricts clinical applications. 2-Hydroxymethyl-3,5,6-trimethylpyrazine (HTMP) is the principal active metabolite of TMP, with similar activity of TMP.

Growth-inhibitory and apoptosis-inducing effects of tanshinones on hematological malignancy cells and their structure-activity relationship.

This study has investigated the growth-inhibitory and apoptosis-inducing effects of dihydrotanshinone, tanshinone I, tanshinone IIA, and cryptotanshinone on hematological malignancy cell lines, aiming to explore their structure-activity relationship. The growth-inhibitory effects of the tanshinones on K562 and Raji cells were assessed using a modified MTT assay; the apoptosis-inducing effects were assessed by fluorescence microscopy and flow cytometry analysis. The changes in cellular morphology were observed using an inverted phase-contrast microscope.

Formulation optimization of prostaglandin E₁-loaded lipid emulsion: enhanced stability and reduced biodegradation.

The purpose of this study is to develop a new formulation for prostaglandin E₁ (PGE₁)-loaded lipid emulsion (Lipo-PGE₁) with improved stability and reduced biodegradation. High-pressure homogenization was used to prepare the Lipo-PGE₁, and high-performance liquid chromatography and accelerated test were used to evaluate its physicochemical stability. A tissue homogenate incubation test was firstly established and validated to assess its biodegradation.

Development of intravenous lipid emulsion of tanshinone IIA and evaluation of its anti-hepatoma activity in vitro.

The purpose of this study was to develop a lipid emulsion of tanshinone IIA (Tan IIA-LE) for intravenous administration and to investigate its feasibility for future clinical practice. The formulation was optimized using central composite design-response surface methodology (CCD-RSM), and the homogenization process was investigated systematically. The Tan IIA-LE was evaluated in terms of stability, safety and in vitro anti-hepatoma activity.

[Inhibitory effect of tanshinones on proliferation of K562 cell line and its structure-activity relationship].

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.

Development of glycyrrhetinic acid-modified stealth cationic liposomes for gene delivery.

The glycyrrhetinic acid-modified stealth cationic liposomes (GA-PEG-CLs) loaded with pDNA (GA-PEG-CLPs) were developed and found to transfect human hepatocellular carcinoma cell line HepG2 with high efficiency. GA-PEG-CLs were comprised of DOTAP, cholesterol (Chol) and glycyrrhetinic acid-polyethyleneglycol-cholesterol conjugate (GA-PEG-Chol). Agarose gel electrophoresis revealed that 5% GA-PEG-CLs constituted by DOTAP/Chol/GA-PEG-Chol at molar ratio of 50:45:5 could completely entrap pDNA at a lower liposomes/pDNA weight ratios of 4:1 (N/P ratio: 1.

[Preparation and quality evaluation of intravenous tanshinone II (A) emulsion].

Objective: To prepare and evaluate an intravenous emulsion of tanshinone II(A).

Method: Soybean phospholipid mixing with poloxamer 188 was used as emulsifier. Oleic acid and glycerol were used as co-emulsifier and isoosmotic adjusting agent, respectively.

[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].

Objective: 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.

Method: HPLC was used to determine the drug concentration in rat plasma and mice tissues after intravenous (i.v.

Preparation, characterization and uptake by primary cultured rat hepatocytes of liposomes surface-modified with glycyrrhetinic acid.

3-succinyl-30-stearyl glycyrrhetinic acid (Suc-GLAOSt) was synthesized as a targeting molecule, and incorporated in ordinary to liposomes (LP) to prepare a liposome surface-modified with glycyrrhetinic acid (LP-GLA), which could bind to the hepatocyte through the specific binding site of glycyrrhetinic acid (GLA) on the surface of rat cellular membrane. The maximal molar ratio of Suc-GLAOSt to total lipids in LP-GLA was 1:10. Calcein loaded liposome (Cal-LP) and calcein loaded LP-GLA (Cal-LP-GLA) were prepared by an ethanol injection method.

Ion-pair reversed-phase HPLC method for determination of sodium tanshinone IIA sulfonate in biological samples and its pharmacokinetics and biodistribution in mice.

The ion-pair reversed-phase HPLC method for determination of sodium tanshinone IIA sulfonate (STS) in various biological samples was for the first time developed and validated, and was applied for pharmacokinetics and tissue distribution studies of intravenously administrated STS in mice. A linear relation was found between peak area and STS concentrations within the ranges of 0.1-5 micraog/ml for plasma, 0.

[Studies on characteristics of absorption and separation of traditional Chinese medicine compound prescription by macroporous resin].

Objective: Study the characteristics of absorption and separation of traditional Chinese medicine compound prescription using macroporous resin.

Method: 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.

Result: 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.

[Tumor cell targetability of folate receptor-mediated mitoxantrone albumin nanoparticles].

Objective: To study the tumor cell targetability of folate-conjugated mitoxantone-loaded albumin nanoparticles (MTO-BSANP-folate).

Methods: Bovine albumin nanoparticles were prepared by desolvation method. The activated folic acid (N-hydroxysuccinimide ester of folic acid) was conjuated to the surface of BSANP via the amino groups.

Uptake of albumin nanoparticle surface modified with glycyrrhizin by primary cultured rat hepatocytes.

Aim: To investigate the uptake difference between bovine serum albumin nanoparticle (BSA-NP) and bovine serum albumin nanoparticles with their surface modified by glycyrrhizin (BSA-NP-GL) and to develop a novel hepatocyte targeting BSA-NP-GL based on active targeting technology mediated by specific binding site of GL on rat cellular membrane.

Methods: Calcein loaded bovine serum albumin nanoparticles (Cal-BSA-NP) were prepared by desolvation process. Glycyrrhizin was conjugated to the surface reactive amino groups (SRAG) of Cal-BSA-NP by sodium periodate oxidization, which resulted in calcein-loaded bovine serum albumin nanoparticles with their surface modified by glycyrrhizin (Cal-BSA-NP-GL).

[Preparation of liposomes surface-modified with glycyrrhetinic acid targeting to hepatocytes].

Objective: To study the preparation of liposomes surface-modified with glycyrrhetinic acid targeting to hepatocytes.

Method: 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.

Result: Targeting molecules can be mixed into the liposomal membrane.

[Study on the tumor cell targetability of folate-conjugated albumin nanoparticles].

Objective: To study folate-conjugated albumin nanoparticles targeting to tumor cells via folate receptor-mediated endocytosis.

Methods: The activated folic acid (N-hydroxysuccinimide ester of folic acid) was conjuated to the surface of bovine serum albumin nanoparticles (BSANP) via the amino groups. The extent of the influence that concentration, incubation time and free folate exerted on the uptake of Folate-BSANP by ovarian cancer cells (SKOV3) was determined using fluorescence spectrophotometer.