Zhang Xinxin, Pan Weisan, Gan Li, Zhu Chunliu, Gan Yong, Nie Shufang
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China.
Chem Pharm Bull (Tokyo). 2008 Dec;56(12):1645-50. doi: 10.1248/cpb.56.1645.
Nanostructured lipid carriers (NLC) are based on mixture of solid lipids with spatially incompatible liquid lipids, which offer advantages of improving drug loading capacity and release properties. In the present study, hydroxycamptothecin (HCPT) loaded polyethylene glycol (PEG) modified NLC (PEG-NLC) was prepared by high pressure homogenize and spray drying method. PEG-NLC showed spherical particle with smooth surface in scanning electron microscopic (SEM) analysis. The crystallinity of lipid matrix within PEG-NLC was evaluated by powder X-ray diffraction and differential scanning calorimetry (DSC). The less ordered crystals or amorphous state of matrix were found in nanoparticles. A small, homogeneous particle size and high drug loading with fine entrapment efficiency of HCPT was obtained in PEG-NLC system. HCPT releasing from PEG-NLC showed a sustained release trend, and no significantly difference was found between two release curves of PEG-NLC before or after spray drying. After storage for 6 months, PEG-NLC powder after spray drying showed no significantly changes in particle size, drug loading and entrapment efficiency, crystal form and in vitro release. PEG modification statistically decreased the phagocytosis of NLC by RAW 264.7 cells, and spray drying process did not influence the cellular uptake of PEG-NLC. These results suggest that PEG-NLC prepared by spray drying is a stable and high-performance delivery system for HCPT.
纳米结构脂质载体（NLC）基于固体脂质与空间不相容液体脂质的混合物，具有提高药物负载能力和释放特性的优势。在本研究中，采用高压均质和喷雾干燥法制备了负载羟基喜树碱（HCPT）的聚乙二醇（PEG）修饰的NLC（PEG-NLC）。扫描电子显微镜（SEM）分析显示PEG-NLC呈表面光滑的球形颗粒。通过粉末X射线衍射和差示扫描量热法（DSC）评估PEG-NLC内脂质基质的结晶度。在纳米颗粒中发现基质的晶体有序度较低或呈无定形状态。PEG-NLC体系获得了小而均匀的粒径、高药物负载量以及HCPT良好的包封效率。PEG-NLC的HCPT释放呈现出缓释趋势，喷雾干燥前后的两条释放曲线之间未发现显著差异。储存6个月后，喷雾干燥后的PEG-NLC粉末在粒径、药物负载量、包封效率、晶型和体外释放方面均未出现显著变化。PEG修饰在统计学上降低了RAW 264.7细胞对NLC的吞噬作用，且喷雾干燥过程不影响PEG-NLC的细胞摄取。这些结果表明，喷雾干燥制备的PEG-NLC是一种稳定且高性能的HCPT递送系统。
