粒径差异化的纳米脂质载体的制备和表征

利用特色化的中心复合设计，以香豆素-6为模型药物，通过控制特定的因素和指标，制备粒径不同而其他性质相同的纳米脂质载体(NLCs)，并对其形态、Zeta电位和包封率等理化性质进行研究。通过体外稳定性实验考察NLCs在K-R液和PBS缓冲液中的稳定性，同时以透析法研究制剂的体外释药行为特性。采用MTT法研究空白NLCs和载药NLCs的细胞毒性，活体成像技术考察NLCs在小鼠胃肠道中的滞留时间。结果显示:制备所得的粒径分别为100，200及300 nm的香豆素-6纳米脂质载体，分散性良好，在K-R液和PBS缓冲液中可以稳定存在，并且体外24 h香豆素-6的累积释放量均不超过总量的7%。MTT实验表明:空白NLCs和载药NLCs对Caco-2毒性较小。小鼠肠内滞留试验显示:NLCs在灌胃给药6 h后仍然能够在胃肠道中检测到。因此，制备得到的不同粒径NLCs可以作为模型制剂，用于细胞水平和动物水平上研究NLCs粒径对口服吸收的影响。
To construct nanostructured lipid carriers(NLCs)with different particle sizes but the same other physicochemical properties, central composite design was adopted. Coumarin-6(C-6)was selected as the model drug due to its high lipophilicity and high fluorescence intensity. Physicochemical properties of NLCs with 100 nm, 200 nm and 300 nm in particle size could remain stable during certain time in K-R solution and PBS. Release experiments in vitro showed that cumulative release of C-6 in NLCs was less than 7% after 24 h. The MTT assay indicated that both blank NLCs and C-6 loaded NLCs showed low toxicity. To confirm the integrity of NLCs in gastrointestinal tract, DiR-loaded NLCs were prepared and the distribution in vivo was monitored by fluorescence imaging. After 6 h oral administration, intact DiR-loaded NLCs could stiu be found, suggesting that NLCs could be used to characterize the uptake in gastrointestinal tract