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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。
10-Hydroxycamptothecin (HCPT) is a broad-spectrum anti-cancer drug, however, its use is limited due to its poor solubility and instability. In this study, hydroxy-camptothecin Nano suspension (HCPT-NSP), also known as nanocrystals, was prepared by micro-precipitation combined with high-pressure homogenization. The drug loading was significantly increased (36.5 ± 9.5 )%, The drug concentration reached (1.35 ± 0.2) mg / m L, higher than HCPT solubility of more than 1000 times. The particle size of HCPT-NSP was (129.8 ± 13.9) nm by dynamic light scattering (DLS). Transmission electron microscopy (TEM) observation of HCPT-NSP was short rod-shaped crystals. X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and differential thermal analysis (DTA) showed that HCPT was short rod-shaped in suspension. HCPT-NSP was intravenously administrated at a dose of 10 mg / kg in vivo. The HCPT-NSP distribution was in line with the three-compartment model. Compared with the pharmacokinetic data after intravenous administration of HCPT injection in the literature, the half-life of HCPT-NSP was prolonged, It is a very promising drug delivery system.