Pharmacochemistry Department, Faculty of Pharmacy, University of Messina, V.le Annunziata, 98168 Messina, Italy.
Biomed Microdevices. 2011 Oct;13(5):799-807. doi: 10.1007/s10544-011-9550-6.
This study investigates the potential of chitosan microspheres as delivery systems for the anticancer drug gemcitabine. The microspheres were obtained by spray-drying chitosan-gemcitabine solutions containing different amounts of the polyanion dextran sulphate. Morphological characterization by SEM and FIB analyses showed the presence of porous spherical particles having sizes ranging from about 1 to 5 μm. Dextran sulphate improves the technological parameters of the systems by producing very high encapsulation efficiency (about 96%, w/w) and by influencing the in vitro release of gemcitabine. The immediate drug release observed in the system prepared without dextrane sulphate (complete drug release within 30 min) was somewhat reduced by the polyanion (immediate release of 70% (w/w) of the encapsulated drug within 30 min, and subsequent continued release of the remaining 30% of the drug for over 4 days). The anti-tumoral efficacy of the various formulations was tested in vitro on human lung cancer cells (A549) comparing the effects with those of the free drug or drug/dextran sulfate complex. The carriers improved the cytotoxic activity of the drug, particularly the formulation containing the lowest amount of dextran sulphate after 72 h incubation.
本研究探讨了壳聚糖微球作为抗癌药物吉西他滨传递系统的潜力。通过喷雾干燥壳聚糖-吉西他滨溶液获得了微球，该溶液中含有不同量的聚阴离子硫酸葡聚糖。SEM 和 FIB 分析的形态特征表明，存在多孔球形颗粒，尺寸约为 1 至 5 μm。硫酸葡聚糖通过产生非常高的包封效率（约 96%，w/w）和影响吉西他滨的体外释放，改善了系统的技术参数。在没有葡聚糖硫酸盐的系统中观察到的立即药物释放（在 30 分钟内完全释放药物）被聚阴离子稍微降低（在 30 分钟内立即释放包裹药物的 70%（w/w），随后在超过 4 天的时间内继续释放剩余的 30%药物）。在体外用人肺癌细胞（A549）上测试了各种制剂的抗肿瘤功效，将其与游离药物或药物/葡聚糖硫酸盐复合物的效果进行了比较。载体提高了药物的细胞毒性活性，特别是在孵育 72 小时后含有最低量硫酸葡聚糖的制剂。
