[Investigation of polyanhydride-glucan as stem cell carriers].

UNLABELLED: The purpose of this study with regard to the effects of polyanhydride--three-dimensional vector-glucan material on the fetal liver stem cell adhesion and proliferation was to find a new carrier. The methods of two-step collagenase perfusion digestion and liquid Percoll discontinuous density gradient centrifugation were used for the separation of fetal liver stem cells. The fetal liver stem cells were selected and cultivated in the polyanhydride-three-dimensional vector-glucan material. Inverted microscope was used to observe cell adhesion and growth status. Also performed were: Calculation of the rate of cell adhesion; MTT assay of the cells in each group absorbance value (OD value); collecting and counting the cells on the carrier scaffold. Then the cell carriers histological sections (HE staining) were observed. On the 7th day of cell culture, the cells were subjected to immunofluorescence staining and flow cytometry. RESULTS: polyanhydride-three-dimensional vector-glucan promoted liver stem cells growth and adhesion. There were active functions of the liver stem cells within carrier materials. In the three-dimensional surface and the internal culture of liver stem cell, proliferation was sustained. After 40 days, the polyanhydride co-culture-three-dimensional vector-glucan showed no sign of toxicity to stem cells. Human fetal liver stem cells attached to the polyanhydride--three-dimensional vector-glucan stent. The cell proliferation went on well and exhibited sustained expression of markers; 7 days training led up to an increase of 19.7 percent in the number of cells. Conclusively, polyanhydride-three-dimensional vector-glucan can be used for promoting the proliferation of liver stem cells, and liver stem cells can be used as vectors in liver tissue engineering.

[Preparation of the EPC and HEPC sterically stabilized doxorubicin liposomes and further studies on pharmacokinetics in rats].

In this paper, we address the preparation of the EPC and HEPC sterically stabilized doxorubicin liposomes and report the data collected from further studies on pharmacokinetics in blood for choosing a better carrier in delivering the drugs. The pharmacokinetics of EPC and HEPC sterically stabilized liposomes (EPC-SSL, and HEPC-SSL) in Wistar rats were investigated by HPLC. The results showed that the mean residence time of HEPC-SSL in blood is 23.3 h, while that of EPC-SSL is 12.0 h. In conclusion, HEPC-SSL is a better carrier in delivering the drugs to the extravascular sites when compared with EPC-SSL.

Fabrication of polystyrene microscale porous substrate and its effects on HL-7702 cells behaviors.

A novel polystyrene (PS) substrate with microscale porous structure was facilely fabricated by crystalline-controlled casting method using mixed solvent [N,N-dimethylformamide and ethyl alcohol (v/v)] based on the nonsolvent induced phase separation process. The substrate surfaces exhibited a bi-continuous microscale porous morphology with high porosity, large pore size and pore-pore connection structure. Moreover, behaviors of the normal human liver cell line (HL-7702) seeded on this substrate surface were carefully investigated. The results indicated that the cell adhesion, spread and cell-cell connection on the surface with subcellular pore size (∼ 10 µm) were similar to the cells proliferated on the flat PS surface. However, the number of HL-7702 cells proliferated on the PS microscale porous surface was higher than cells on the conventional PS flat surface, suggesting that the pore-pore structure was conducive to HL-7702 cell proliferation. Furthermore, hematoxylin and eosin staining and micronucleus test were performed. The results showed that fewer damages for nuclear and cytoplasm and less cell genotoxicity were caused by the microscale porous structure within the scope of pore size (∼ 10 µm) than that of the flat surface.

Clinical pharmacokinetics of paclitaxel liposome with a new route of administration in human based on the analysis with ultra performance liquid chromatography.

We investigated the clinical pharmacokinetics of paclitaxel liposome with a new route of administration, which was intrapleural infusion, in nine advanced nonsmall-cell lung cancer (NSCLC) patients with malignant pleural effusions after a single administration. Paclitaxel concentrations were measured in pleural fluid and plasma using a simple and rapid ultra performance liquid chromatography (UPLC) method following intra- and inter-day validations. In subjects, AUC(0-96 h) values in pleural fluid and plasma were 17831 ± 6439 µg h/mL and 778 ± 328 µg h/mL, respectively, and T(max) values were initial time and 6.67 h after administration and the corresponding C(max) values were 558 ± 44 µg/mL and 12.89 ± 6.86 µg/mL, respectively. The T(1/2,IP), CL(IP) and Vd(IP) values in pleural fluid were 76 ± 48 h, 0.005 ± 0.002 L/h m(2) and 0.53 ± 0.23 L/m(2), respectively. The T(1/2,pla), CL(pla), and Vd(pla) values in plasma were 68.34 ± 56.74 h, 0.184 ± 0.080 L/h m(2), and 17.53 ± 16.57 L/m(2), respectively. However, some paclitaxel concentrations from several patients in plasma could not be detected at some designed time-points. Our results might offer new opportunities to design and determine individually appropriate therapeutic dosage regimens based on a pharmacokinetic profile.

A phase I clinical and pharmacokinetic study of paclitaxel liposome infused in non-small cell lung cancer patients with malignant pleural effusions.

PURPOSE: To investigate the feasibility, pharmacokinetics, efficacy and toxicity of intrapleural paclitaxel liposome injection in non-small cell lung cancer (NSCLC) patients with malignant pleural effusions. PATIENTS AND METHODS: Twelve of 15 NSCLC patients with malignant pleural effusions were treated with paclitaxel liposome and three were treated with free paclitaxel. Adequate pleural fluid, blood and urine were collected for pharmacokinetic study. The clinical efficacy and toxicity were synthetically evaluated according to the correlative criteria. RESULTS: The overall toxicity of paclitaxel liposome was lower than that of free paclitaxel. In the patients treated with paclitaxel liposome, there were minimal local chest pain, anaphylaxis, anaemia, neutropaenia and hepatotoxicity. The complete response rates of pleural effusion at the first, second, third and sixth month were, respectively, 27.3%, 18.2%, 9.1% and 9.1%, and overall response rates were 90.9%, 72.7%, 63.6% and 54.5%, respectively. Pharmacokinetic study showed that mean C(max,IP), T(1/2) and AUC(0-->96,IP) in pleural fluid were, respectively, about 2-fold, 2-fold and 2.5-fold than those of free paclitaxel, and AUC(0-->96,Pla) in plasma was also much higher than that of free paclitaxel, however, excretory rate in 24h from urine was lower than that of free paclitaxel. CONCLUSIONS: This study demonstrated that paclitaxel liposome was a more useful agent than free paclitaxel for the treatment of malignant pleural effusions because of its relatively low toxicity and distinct pharmacokinetic characteristics. The phase II study of a large number of patients was recommended to confirm this finding.