Preparation,characterization and pharmacokinetics of 10-hydroxycamptothecin nanosuspension

10-羟基喜树碱纳米混悬剂的制备、表征和药物动力学评价（英文）

10-Hydroxycamptothecin （HCPT） is a broad-spectrum anticancer drug, while its low solubility and instability severely limit its application. In this study, HCPT nanosuspension （HCPT-NSP）, also known as nanocrystal, was prepared by micro-precipitation combined with high-pressure homogenization method. This nanosuspension was characterized by size, shape, zeta potential, drug loading efficiency and in vitro drug release behavior. Preferred formulation and process showed that particle size was （129.8±13.9） nm, PDI was 0.20±0.07, and drug loading efficiency was 36.5%±9.5%. Moreover, HCPT nanocrystal concentration reached （1.35±0.2） mg/mL in HCPT-NSP, which was more than 1000-fold higher than that of HCPT. Transmission electron microscopy （TEM） results showed that the nanosuspension was short rod in shape. X-ray powder diffraction （XRD）, thermogravimetric analysis （TGA）, derivative thermogravimetric analysis （DTA） and differential scanning calorimetry （DSC） further elaborated the crystal state of the HCPT. The drug concentration-time curve of HCPT-NSP in rats was in accordance with the three-compartment model, showing prolonged half-life. Taken together, our data suggested that HCPT-NSP was a promising drug delivery system.

10-羟基喜树碱(HCPT)是一种广谱抗癌药,然而由于其溶解性差、不稳定,限制了它的应用。本研究采用微沉淀法联合高压均质法制备羟基喜树碱纳米混悬剂(HCPT-NSP),也称为纳米晶体,显著提高了HCPT的载药量,药物包载率为(36.5±9.5)%,药物浓度达到(1.35±0.2)mg/m L,高于HCPT溶解度的1000倍以上。用动态光散射法(DLS)测定HCPT-NSP粒径为(129.8±13.9)nm。透射电镜(TEM)观察HCPT-NSP呈短杆状晶体。X射线粉末衍射(XRD)和差示扫描量热法(DSC)、热重分析(TGA)、微分热重分析(DTA)结果显示,HCPT在混悬剂中呈短杆状晶体状态。HCPT-NSP以10 mg/kg剂量静注后在体内分布符合三房室模型,与文献中HCPT注射液静脉给药后的药物动力学数据相比,HCPT-NSP的半衰期延长,预示HCPT-NSP是一种很有前景的给药体系。