Preparation and quality evaluation of comet-shaped hydroxy camptothecin-loaded amphiphilic block copolymer / 药学学报

In this study, we used Shirasu porous glass membrane (SPG) as a template and hydroxy camptothecin (HCPT) as a model drug to prepare the comet-shaped MePEG[methoxyl poly(ethylene glycol)]-PLGA[poly(lactic-co-glycolic acid)-HCPT amphiphilic block copolymer. Our method was optimized by the orthogonal design method. The partical size, zeta potential, drug-loaded content, yield, shape and status of the obtained comet-shaped MePEG-PLGA-HCPT particles were further characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM)/transmission electron microscopy (TEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) et al, respectively. In vitro release was preliminary evaluated. MTT assay to preliminary evaluate the cytotoxicity of particles against human liver BEL-7402 cells. Based on these experimental results, the optimal preparation conditions contain:weight ratio of HCPT to MePEG-PLGA was 1:1, nitrogen pressure was 100 kPa and SPG membrane pore size was 1.1 μm. The particles exhibited a comet-shaped shape, fairly uniform size and were well dispersed. The drug-loading content was 46.2%, with yield of 96.4%, and zeta -31.4 mV. The distribution of HCPT in particles was very uniform, and HCPT showed a amorphous state existed in particles. The release behavior in vitro showed sustained releasing,and with the drug loading content in proportion to the release of the drug. MTT test indicated that the HCPT-loaded comet-shaped particles had enhanced the cytotoxicity against human liver BEL-7402 cells relatively to the HCPT-loaded spherical particles in vitro. The results showed a promising potential application of the preparation in clinical treatment of tumor.

Effect of curcumin on the induction of glutathione S-transferases and NADP(H):quinone oxidoreductase and its possible mechanism of action / 药学学报

This study is to investigate the effect of curcumin on the induction of glutathione S-transferases (GST) and NADP(H):quinone oxidoreductase (NQO) and explore their possible molecular mechanism. The activity of GST, NQO and cellular reduced glutathione (GSH) content were measured by spectrophotometrical methods. Cellular changes in the distribution of NF-E2 related factor 2 (Nrf2) were detected by Western blotting analysis. Nrf2-AREs (antioxidant-responsive elements) binding activity was examined by electrophoretic mobility shift assay (EMSA). Treatment of HT-29 human colon adenocarcinoma cells with curcumin dramatically induced the activity of GST and NQO at the range of 10-30 micromol x L(-1). Curcumin exposure caused a significant increase in cellular GSH content rapidly as early as 3 h. Moreover, curcumin triggered the accumulation of Nrf2 in nucleus, and increased Nrf2 content in ARE complexes. These results demonstrated that induction of GST and NQO activity by curcumin may be mediated by translocation of transcription factor Nrf2 from cytoplasm to nuclear and increased binding activity of Nrf2-ARE complexes.

Treatment of hepatocellular carcinoma in mice with locally administered epirubicin-loaded poly(D, L)-lactic acid microspheres / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effectiveness of treating hepatocellular carcinoma (HCC) in mice with locally administered epirubicin-loaded poly( D, L) - lactic acid microspheres (EPI-PLA-MS ).</p><p><b>METHODS</b>EPI-PLA-MS was prepared with double emulsion solvent evaporation technique. Five groups of mice (n = 8 in each group) were intraperitoneally injected with five different doses of free epirubicin (FEPI), and the maximum tolerated dose (MTD) was calculated. Then 15 mice with transplanted subcutaneous H22 HCC were divided into three groups (n = 5), which were respectively intratumorally injected with normal saline (NS), blank microspheres, and EPI-PLA-MS (with 9 mg/kg of EPI). After two weeks the tumors were excised and weighed. Another 15 mice with transplanted H22 ascites HCC were divided into three groups (n = 5), which were intraperitonealy injected with the same drugs, and the increased life span were registered exactly.</p><p><b>RESULTS</b>The MTD of intraperitoneally injected FEPI was 9 mg/kg. The tumour-inhibiting rates was 40.35% and 36.09% when EPI-PLA-MS were administered by intratumoral injection to the mice with subcutaneous H22 HCC. It significantly prolonged the survival time of mice with H22 ascites HCC and the increased life span by 153.49% and 142.22% when EPI-PLA-MS were intraperitoneally administered.</p><p><b>CONCLUSION</b>EPI-PLA-MS is a new sustained-release preparation with high-efficacy and low-toxicity in treating HCC and has shown promising prospects when administered locally.</p>

The stability of insulin-loaded polybutylcyanoacrylate nanoparticles in an oily medium and the hypoglycemic effect in diabetic rats / 药学学报

<p><b>AIM</b>To study the stability of insulin-loaded polybutylcyanoacrylate nanoparticles (IPN) in an oily medium (soybean oil containing 0.5% (v/v) Tween-20 and 5% (v/v) Vitamin E) along with the hypoglycemic effect following their oral administration to streptozotocin (STZ) induced diabetic rats.</p><p><b>METHODS</b>The stability of IPN in the process was appraised by measurement of the amount of undegraded insulin associated to nanoparticles, the average size and the span of IPN, as well as the release of insulin from IPN. IPN in an aqueous medium (containing 0.5% (v/v) Tween-20) at pH 2.0 was also investigated as control.</p><p><b>RESULTS</b>The study showed that IPN in the oily medium was more stable than that in the aqueous medium over one year of storage in the dark at (25 +/- 2) degrees C and the in vitro stability of IPN in the oily medium against degradation by proteolytic enzymes was much better than that in the aqueous medium. The apparent bioavailability of an oral administration of IPN (50 u x kg(-1)) in the oily medium versus an (sc) injection of insulin (2 u x kg(-1)) was 22.4%, much higher than that of IPN in the aqueous medium (15.5%), based on decreased areas above curve (AAC) determination for the blood glucose depression from time zero to 144 h of a single oral administration of IPN to STZ-diabetic rats.</p><p><b>CONCLUSION</b>IPN in soybean oil containing Tween-20 (0.5% v/v) and Vitamin E (5% v/v) could be considered as an effective and stable delivery system for oral insulin.</p>