TIFAC- Centre of Relevance and Excellence in NDDS, Pharmacy Department, The M. S. University of Baroda, Gujarat, India.
Curr Drug Deliv. 2010 Jan;7(1):51-64. doi: 10.2174/156720110790396517.
Etoposide is one of the most commonly used drugs in chemotherapy of acute lymphocytic leukemia and acute myelogenous leukaemia. Etoposide has variable oral bioavailability ranging from 24-74% and has terminal half life of 1.5 hours by intravenous route. The conventional parenteral therapy causes inconvenience and pain to the patients as it has to be given through a continuous IV infusion over 24-34 h. The present investigation was aimed at developing etoposide loaded biodegradable nanoparticles which would be a sustained release formulation and replace the conventional therapy of continuous intravenous administration. Nanoparticles were prepared by emulsion solvent evaporation method using high pressure homogenization. The process parameters like homogenization cycles (four) and homogenization pressure (10000 psi) were first optimized using a 3(2) factorial design based on response Y1(mean particle size of 98+/-1nm). Then a 32 factorial design was carried out to study the effect of two independent variables, ratio of drug and polymer (X1) and surfactant concentration (X2) on the two responses to obtain their optimized values, percentage entrapment efficiency (Y2, 83.12+/-8.3%) and mean particle size (Y3, 105+/-5.4 nm) for Etoposide loaded PLGA Nanoparticles. Contour plots and response surface plots showed visual representation of relationship between the experimental responses and the set of input variables. The adequacy of the regression model was verified by a check point analysis. The zeta potential values ranged between -23.0 to -34.2 mV, indicating stability. Sucrose was used as cryoprotectant during lyophilization. DSC and XRD studies indicated that etoposide was present in the amorphous phase and may have been homogeneously dispersed in the PLGA matrix. The electron micrographs showed spherical, discrete and homogenous particles. Drug release study showed that etoposide loaded PLGA nanoparticles sustained release up to 72h. The release from the nanoparticles followed first order kinetics and mechanism of drug release was Fickian. Stability studies indicated that it was best to store nanoparticle formulations in the freeze dried state at 2-8 degrees C where they remained stable in terms of both size and drug content upto three months.
依托泊苷是急性淋巴细胞白血病和急性髓性白血病化疗中最常用的药物之一。依托泊苷的口服生物利用度变化范围为 24-74%，静脉给药的终末半衰期为 1.5 小时。传统的肠外治疗给患者带来了不便和痛苦，因为它必须通过 24-34 小时的连续静脉输注给予。本研究旨在开发依托泊苷负载的可生物降解纳米粒，这将是一种缓释制剂，可以替代传统的连续静脉给药治疗。纳米粒采用乳化溶剂蒸发法，高压匀浆法制备。首先，通过基于响应 Y1（平均粒径为 98+/-1nm）的 3(2)因子设计优化了工艺参数，如匀浆循环（4 次）和匀浆压力（10000psi）。然后进行了 32 因子设计，以研究两个独立变量，药物与聚合物的比例（X1）和表面活性剂浓度（X2）对两个响应的影响，以获得其优化值，依托泊苷负载 PLGA 纳米粒的包封率（Y2，83.12+/-8.3%）和平均粒径（Y3，105+/-5.4nm）。等高线图和响应面图直观地显示了实验响应与设定输入变量之间的关系。通过检查点分析验证了回归模型的充分性。Zeta 电位值在-23.0 至-34.2mV 之间，表明稳定性。在冷冻干燥过程中使用蔗糖作为冷冻保护剂。DSC 和 XRD 研究表明，依托泊苷处于无定形相，可能均匀分散在 PLGA 基质中。电子显微镜照片显示出球形、离散和均匀的颗粒。药物释放研究表明，依托泊苷负载的 PLGA 纳米粒可在 72 小时内持续释放。纳米粒的释放遵循一级动力学，药物释放机制为菲克扩散。稳定性研究表明，最好将纳米粒制剂在 2-8°C 的冷冻干燥状态下储存，在三个月内，它们在大小和药物含量方面都保持稳定。
