Biphasic dissolution test and its application in the evaluation of poorly soluble drug preparations / 药学学报

Biphasic dissolution test, consisting of immiscible aqueous and organic phase, is an in vitro dissolution method that simultaneously measures the dissolution and partition of drugs. Due to the advantages of simulating in vivo absorption and overcoming the influence of surfactants on dissolution, it has been widely used to evaluate the poorly soluble drugs in vitro dissolution. Based on the relevant research in this field in recent years, this review summarizes the history, dissolution device, theoretical model and application of the biphasic dissolution test. Finally, the prospects in the development of biphasic dissolution test are also outlined.

Synthesis and characterization of N,N-dimethyl-(N',N'-di-stearoyl-1-ethyl) 1,3-diaminopropane as drug delivery system of methotrexate / 中国药学杂志

OBJECTIVE: To synthesize a novel cationic lipid,N,N-dimethyl-[N',N'-di-(stearoyl-1-ethyl)] 1,3-diaminopropane (DMSP),and evaluate its feasibility as methotrexate(MTX) carrier. METHODS: DMSP and phosphatidylcholine were employed to prepare liposomes by reverse phase evaporation method,and then MTX was entrapped by physical mixing. The entrapment efficiency was determined by ultracentrifugation,and its release ratio was evaluated by dialysis. The morphology of liposomes was observed under transmission electron microscope. The average diameter and Zeta potential were determined by laser particle size analyzer. MTT test was used to evaluate the cytotoxicity of liposomes as drug carrier and the inhibition of cancer cells growth. RESULTS: The obtained liposomes showed regular shape and uniform size,with a mean Zeta potential of +(36.26±4.77)mV and average diameter of 120 nm. The liposomes had low hemolytic activity and cytotoxicity. With the help of DMSP the cationic liposomes achieved a very high entrapment efficiency for the hydrophilic drug MTX (91.50±1.02)%. The inhibition of the MTX liposomes on cancer cells growth was much higher than that of MTX solution. CONCLUSION: DMSP is a novel cationic lipid with low cytotoxicity and high entrapment efficiency,which has a great application potential in drug delivery system.

Synthesis and characterization of N-(N',N'-Dimethyl) propyl succinic mono-cholesteryl mono-amide as gene carrier / 中国药学杂志

OBJECTIVE: To synthesize a novel cationic cholesterol derivative, N-(N',N'-dimethyl) propyl succinic mono-cholesteryl mono-amide (DMAPA-CHEMS), and evaluate its feasibility as a none-viral gene vehicle. METHODS: DMAPA-CHEMS and phospholipid were employed to produce liposomes by thin membrane dispersion method, and the morphology of liposomes was observed under transmission electron microscope. The average diameter and Zeta potential were determined by laser particle size analyzer. The combination to and protection for DNA were investigated via agarose gel electrophoresis. The uptake of FITC-labelled oligonucleotides into HepG2 cells was determined by flow cytometry, while the transfection promotion of liposomes for GFP-plasmid DNA was observed by inverted fluorescence microscope. RESULTS: The obtained liposomes showed regular shape and uniform size, with a mean diameter of 94.0 nm and Zeta potential of 24 mV. The liposomes could combine DNA completely and protect DNA from the degradation of DNase I when the charge ratio of cationic cholesterol to DNA was more than 4. The cationic liposomes had low cytotoxicity. Although the uptake efficiency of liposomes made of DMAPA-CHEMS was lower than that of DC-Chol, the gene expression efficiency was higher. CONCLUSION: DMAPA-CHEMS is a novel gene carrier with high transfection efficiency and low cytotoxicity, which has a great potential for application.

The strategies of endosomal escape for intracellular gene delivery / 药学学报

The intracellular trafficking and subcellular distribution of exogenous gene is very important for gene delivery. A successful gene vehicle should overcome various barriers including endosomal membrane barriers to delivery gene to the target organelle. Traditional nonviral vehicle is unable to avoid endosomal pathway efficiently, so the efficiency of gene delivery is low and the application of gene drugs is limited. In order to achieve efficient nonviral gene delivery, a lot of researches based on endosomal escape have been carried out and some agents with the function of endsomal escape have been found. These agents facilitate the endsomal escape via various mechanisms, such as fusion into the lipid bilayer of endosomes, pore formation in the endosomal membrane, proton sponge effect and photochemical methods to rupture the endosomal membrane. In this review, various reported strategies for endsomal escape are described according to the escape mechanisms, and their applications in intracellular gene delivery are also discussed.

Cellular uptake behavior of antisense oligodeoxynucleotides polymethacrylate submicroparticles / 药学学报

<p><b>AIM</b>To survey the uptake behavior and subcellular distribution of antisense oligodeoxynucleotide polymethacrylate submicroparticles (AS-ODN-SMP) and infer its mechanism in MGC cell lines.</p><p><b>METHODS</b>MGC cells were incubated at certain concentration of AS-ODN-SMP or AS-ODN for 8 h at 4 degrees C or 37 degrees C. Then the fluorescence oligodeoxynucleotide- labeled cells were counted by flow cytometer and the intracellular fluorescence intensity was determined after incubated with chloroquine for 2 h.</p><p><b>RESULTS</b>Cellular uptake of oligodeoxynucleotides was significantly increased following application of AS-ODN-SMP and total intracellular fluorescence intensity was enhanced by 683 folds with the vehicle concentration of 20 microg x mL(-1). AS-ODN-SMP entranced to cells profoundly with temperature-dependent manner. Rare cells took on fluorescence when incubated at 4 degrees C, while 37 degrees C they were significantly increased. But the intracellular fluorescence intensity appeared same level in present or absent of chloroquine.</p><p><b>CONCLUSION</b>With the help of polyacrylate submicroparticles, oligonucleotides efficiently entranced the cells via endocytosis and could successfully escape the degradation in lysosome.</p>

Effect of panaxadiol saponin and panaxtrol saponin on proliferation of human bone marrow hemopoietic progenitor cells / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of panaxadiol saponin (PDS) and panaxtrol saponin (PTS) on proliferation of human bone marrow hemopoietic progenitor cells (HPC).</p><p><b>METHODS</b>PDS and PTS were separated and purified from ginsenosides, and the effects on HPC were studied using in vitro hemopoietic progenitor cell colony-forming technique, by observing the proliferation of human burst forming unit-erythroid progenitor (BFU-E), colony-forming unit-erythroid (CFU-E), colony-forming unit-granulocyte/macrophage (CFU-GM) and colony-forming unit-pluripotent hemopoietic progenitor (CFU-Mix) in mice after PDS and PTS stimulation.</p><p><b>RESULTS</b>Different concentration of PDS (2.5-200 micrograms/ml) could stimulate the proliferation of HPC obviously, showing increase of CFU-E, BFU-E, CFU-GM and CFU-Mix by 54.9 +/- 6.3%, 48.8 +/- 5.1%, 27.6 +/- 4.2% and 48.9 +/- 3.9% respectively, which was higher than that of the control group. While stimulated by PTS of the same concentration, the CFU-E and BFU-E was lower than that of control significantly (P < 0.05); when the terminal concentration of PTS was 200 micrograms/ml, CFU-E and BFU-E was zero respectively. In the CFU-GM culture, PTS in concentration of 12.5 micrograms/ml could cause the proliferation increased by 29.7 +/- 2.2% (P < 0.05), but in concentration of 100 micrograms/ml and 200 micrograms/ml, it showed inhibitory effect on CFU-GM, the inhibition rate being 48.6 +/- 3.9% and 100% respectively.</p><p><b>CONCLUSION</b>PDS is the effective component of ginsenosides in stimulating proliferation of human bone marrow HPC. PTS is an component with inhibitory action on proliferation of CFU-E and BFU-E and its effect on CFU-GM was depending on its concentration.</p>

Study on polymethacrylate nanoparticles as delivery system of antisense oligodeoxynucleotides / 药学学报

<p><b>AIM</b>To investigate the possibility of polymethacrylate nanoparticles (NP) for antisense oligodeoxynucleotides delivery system.</p><p><b>METHODS</b>The nanoparticles were prepared by evaporating ethenol solution containing Eudragit RL100 or RS100, and then mixtured with oligonucleotides. The morphology and size were investigated by a transmission electron microscope and Mastersizer particle characterization systems, and the cytotoxicity was evaluated by Trypan Blue staining and hemolysis test. The flow cytometer was used to determine the uptake of fluorescence-labelled oligodeoxynucleotides.</p><p><b>RESULTS</b>The morphology of nanoparticles showed spherical and orderly, the average diameter was about 127 nm, and almost the antisense oligodeoxynucleotides (ODN) were loaded when NP: ODN was 6.6. The uptake of ODN was significantly increased when loaded by nanoparticles, which well depended on the nanoparticles concentration. Meanwhile, slightly cytotoxicity was observed when high dose of nanoparticles was used.</p><p><b>CONCLUSION</b>The polymethacrylate nanoparticles appeared to be a promising vehicle for gene delivery.</p>