Intracellular uptake of nanocrystals: Probing with aggregation-induced emission of fluorescence and kinetic modeling

Nanocrystal formulations have been explored to deliver poorly water-soluble drug molecules. Despite various studies of nanocrystal formulation and delivery, much more understanding needs to be gained into absorption mechanisms and kinetics of drug nanocrystals at various levels, ranging from cells to tissues and to the whole body. In this study, nanocrystals of tetrakis (4-hydroxyphenyl) ethylene (THPE) with an aggregation-induced emission (AIE) property was used as a model to explore intracellular absorption mechanism and dissolution kinetics of nanocrystals. Cellular uptake studies were conducted with KB cells and characterized by confocal microscopy, flow cytometry, and quantitative analyses. The results suggested that THPE nanocrystals could be taken up by KB cells directly, as well as in the form of dissolved molecules. The cellular uptake was found to be concentration- and time-dependent. In addition, the intracellular THPE also could be exocytosed from cells in forms of dissolved molecules and nanocrystals. Kinetic modeling was conducted to further understand the cellular mechanism of THPE nanocrystals based on first-order ordinary differential equations (ODEs). By fitting the kinetic model against experimental measurements, it was found that the initial nanocrystal concentration had a great influence on the dynamic process of dissolution, cellular uptake, and exocytosis of THPE nanocrystals. As the nanocrystal concentration increased in the culture media, dissolution of endocytosed nanocrystals became enhanced, subsequently driving the efflux of THPE molecules from cells.

Effect of different compatibility of tetramethylpyrazine on its pharmacokinetics in vivo / 中国中药杂志

<p><b>OBJECTIVE</b>To study the pharmacokinetics of single administration and different compatibility of tetramethylpyrazine (TMP) in rats.</p><p><b>METHOD</b>Thirty two Sprague-Dawley rats were randomly divided into 4 groups: the TMP (30 mg x kg(-1)) group, the TMP+FA (30 mg x kg(-1) + 50 mg x kg(-1)) group, the TMP+TET (30 mg x kg(-1) mg x kg(-1)) group and the TMP+FA+TET (30 mg x kg(-1) + 50 mg x kg(-1) + 20 mg x kg(-1)) group. After the oral administration, their blood samples were collected to detect plasmas concentrations by HPLC method and to calculate pharmacokinetic parameters DAS 2.0 program.</p><p><b>RESULT</b>In compatibility with FA, AUC(0-t), Cmax and Tmax showed no significant difference with the single administration of TMP, but t(1/2) and MRT,, were obviously longer than the single administration. In compatibility with TET and FA + TET, AUC (0-t), Cmax and Tmax showed significant increase than the single administration of TMP, whereas t(1/2) and MRT0, did not notably vary from the single administration.</p><p><b>CONCLUSION</b>FA can prolong TMP's action time in rats, and TET can accelerate TMP's absorption in rats.</p>

Study on pharmacokinetics of ferulic acid loaded liposome-in-chitosan-microspheres in rats / 中国中药杂志

In this paper, the pharmacokinetics of ferulic acid loaded liposome-in-chitosan-microspheres was investigated. Eighteen Sprague-Dawley rats were divided into 3 groups randomly. Each group was administered orally of ferulic acid, ferulic acid loaded chitosan microspheres and ferulic acid loaded liposome-in-chitosan-microspheres, respectively. Then blood samples were obtained from fossa orbitalis at different time points. The concentration of ferulic acid in blood was analyzed by a HPLC method using coumarin as internal standard. The data were analyzed by DAS program. The t(max), MRT and t(1/2beta) of liposome-in-chitosan-microspheres were 2.500, 7.487 and 7.818 h, respectively, which were much longer than crude drug and chitosan microspheres. This results demonstrated that liposome-in-chitosan-microspheres had better sus-tained-releasing property. The AUC of liposome-in-chitosan-microspheres was 6.08 times higher than crude drug and 1.21 times higher than chitosan microspheres, which verified that liposome-in-chitosan-microspheres could enhance oral absorption.

Preparation and in vitro drug release of ferulic acid loaded chitosan microspheres containing liposomes / 中国中药杂志

<p><b>OBJECTIVE</b>To construct the ferulic acid loaded chitosan microspheres containing liposomes.</p><p><b>METHOD</b>Ferulic acid was selected to be the model drug. Liposomes were prepared by calcium acetate gradient method. The entrapment efficiency of liposomes was(79.97 +/- 0.54)%, the average size was (187.6 +/- 11.9) nm and the Zeta potential was -12.67 +/-1.78. The chitosan microspheres, whose entrapment efficiency was (57.89 +/- 1.72)%, were prepared by onic gelation method after liposomes were mixed with chiotosan solution. Ferulic acid was entrapped in liposomes in amorphous form and then liposomes were distributed in microspheres intactly.</p><p><b>RESULT</b>The 80.97% liposomes were released from microspheres and the 32.33% ferulic acid was released from microspheres at 12 h, which was much slower than simple chitosan microspheres.</p><p><b>CONCLUSION</b>This study demonstrated that chitosan microspheres containing liposomes have good sustained-releasing property in vitro.</p>

Comparative study on pharmacokinetics of tetramethylpyrazine, ferulic acid and their compatibility / 中国中药杂志

<p><b>OBJECTIVE</b>To study the pharmacokinetics of tetramethylpyrazine (TMP), ferulic acid and their compatibility.</p><p><b>METHOD</b>Twenty-four Sprague-Dawley rats were randomly divided into 3 groups: TMP 20 mg x kg(-1), ferulic acid 20 mg x kg(-1) and TMP 20 mg x kg(-1) + ferulic acid 20 mg x kg(-1). All the rats were given intragastric administration then blood samples were obtained from fossa orbitalis at several time points. All the plasmas concentrations were analyzed by HPLC method and the data were treated by DAS 2.0 program.</p><p><b>RESULT</b>The main pharmacokinetics parameters of TMP 20 mg x kg(-1) group, ferulic acid 20 mg x kg(-1) and TMP 20 mg x kg(-1) + ferulic acid 20 mg x kg(-1) were as follows: t(max) 0.5 h, t1/2 0.856 h,MRT 1.321 h, AUC 5.112 microg x h(-1) x L(-1), C(max) 2.834 microg x L(-1); t(max) 0.083 h, t1/2 1.024 h, MRT 1.324 h, AUC 1.581 microg x h(-1) x L(-1), C(max) 1.492 microg x L(-1); t(max) 0.583 h, t1/2 37.901 h, MRT 3.798 h, AUC 4.097 microg x h(-1) x L(-1), C(max)1.571 microg x L(-1); t(max) 0.6 h, t1/2 7.860 h, MRT 2.894 h, AUC 1.984 microg x h(-1) x L(-1), C(max) 1.03 microg x L(-1), respectively.</p><p><b>CONCLUSION</b>The experiments suggested that the compatibility of TMP and ferulic acid had interaction in pharmacokinetics; all the t1/2 and MRT were prolonged and had the effect of lente liberates.</p>

Relationship of tetramethylpyrazine on expression of vascular endothelial growth factor and development of adjuvant-induced arthritis in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the effect of tetramethylpyrazine (TMP) on the expression of vascular endothelial growth factor (VEGF) in the synovium of adjuvant-induced arthritis (AIA) in rats.</p><p><b>METHOD</b>AIA rats were treated with different doses of TMP. The effects of treatment were monitored by footpad thickness, contents of tumor necrosis factor-alpha (TNF-alpha) in serum, microvessel density (MVD) and the expression of VEGF protein in the synovium.</p><p><b>RESULT</b>Compared with arthritis model, 100 mg x kg(-1) TMP could remarkably reduce the footpad thickness, contents of TNF-alpha in serum and the expression of VEGF in the synovium.</p><p><b>CONCLUSION</b>TMP can attenuate the degree of chronic inflammation in AIA rats, and its mechanism might be associated with inhibiting the expression of VEGF.</p>

Preparation of valaciclovir loaded bovine serum albumin nanoparticles surface-modified with glycyrrhizin and its characteristics of targeting to liver / 生物医学工程学杂志

The valaciclovir was used as the model drug, 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 VACV-BSA-NP. Gel filtration method combined with HPLC method verified that GL was covalent coupling to the surface of VACV-BSA-NP with mean 9 GL residues per albumin molecule. The mean diameter of the VACV-BSA-NP-GL was 268 +/- 23 nm, the drug loading was 1.35%, and embedding ratio was 68.76%. The characteristics of release in vitro were in accord with two-phase kinetics. The uptake amount of VACV-BSA-NP-GL by primary cultured rat hepatocytes in vitro was higher, compared to the control-VACV-BSA-NP. 69.89% and 64.82% of the VACV were concentrated in liver at 15 min after i.v. VACV-BSA-NP-GL and VACV-BSA-NP, respectively. There is a significant difference between surface-modified group and control group (P<0.10). VACV-BSA-NP-GL was successfully prepared, which is considered to be a novel drug delivery system for targeting to hepatocytes.

STUDY ON HYPOTENSIVE CONSTITUENT OF RHODODENDRON MOLLE ( BI. ) G.DON / 中国药理学通报

Four constitunets were isolated from the flower of Rhododendron molle ( BI. ) G. Don. One of these was named Rdl.The acute LD50 of Rdl in mice ( iv ) was found to be 4742 ug/kg.The hypotensive effect of Rdl was studied in various anesthesized animals. In cats, the dosage of 100, 300 and 500 Hg/kg of the Rdl ( iv ) reduced the blood pressure by 10:9% ( P