Nanostructured Lipid Carriers (NLC) for Parenteral Delivery of an Anticancer Drug
Nanostructured Lipid Carriers (NLC) for Parenteral Delivery of an Anticancer Drug
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DOI：
10.1208/s12249-011-9733-8
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发表时间：
2012-03-01
影响因子：
3.3
通讯作者：
Opanasopit, Praneet
中科院分区：
文献类型：
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作者：
Chinsriwongkul, Akhayacatra;Chareanputtakhun, Ponwanit;Opanasopit, Praneet
本研究的目的是研制抗癌药物全反式维甲酸(ATRA)肠外给药的纳米脂质载体(NLC)。采用从头乳化法将全反式维甲酸引入NLC。确定了配方因素，即类型和油比、ATRA初始浓度对其理化性能的影响。并研究了负载ATRA的NLC对HL-60和HepG2细胞的抗癌作用。固体脂质(十六烷基棕榈酸酯)和液体脂质(S大豆油、中链甘油三酯(M)、S/油酸(O；3：1)和M/O(3：1)按1：1的重量比混合而成。负载全反式维甲酸的NLC平均尺寸小于200 nm(141.80~172.95 nm)，PDI较窄，负Zeta电位在静脉注射可接受的范围内。结果表明，油酸提高了NLC的ATRA载药量。ATRA的体外释放度在48h内仅为4.06%~4.34%，不同油相组成的NLC制剂的ATRA释放率无显著差异。此外，没有观察到药物的突释，表明NLC可以延长ATRA的释放。药物初始浓度影响光降解速率，但不影响释放速率。所有负载全反式维甲酸的NLC制剂都表现出光保护性能。细胞毒性实验结果表明，所有负载ATRA的NLC细胞毒性均高于游离药物，且HL-60细胞对ATRA的敏感性高于HepG2细胞。
The purpose of this research was to formulate nanostructured lipid carriers (NLC) for the parenteral delivery of an anticancer drug, all-trans retinoic acid (ATRA). The ATRA was incorporated into NLC by the de novo emulsification method. The effect of the formulation factor, i.e., type and oil ratio, initial ATRA concentration on physicochemical properties was determined. The anticancer efficacy of ATRA-loaded NLC on HL-60 and HepG2 cells was also studied. NLC was formulated using a blend of solid lipids (cetyl palmitate) and liquid lipids (soybean oil (S), medium-chain triglyceride (M), S/oleic acid (O; 3:1) and M/O (3:1)) at a weight ratio of 1:1. ATRA-loaded NLC had an average size of less than 200 nm (141.80 to 172.95 nm) with a narrow PDI and negative zeta potential that was within an acceptable range for intravenous injection. The results indicated that oleic acid enhanced the ATRA-loading capacity of NLC. In vitro ATRA release was only approximately 4.06% to 4.34% for 48 h, and no significant difference in ATRA release rate from all NLC formulations in accordance with the composition of the oil phase. Moreover, no burst release of the drug was observed, indicating that NLC could prolong the release of ATRA. The initial drug concentration affected the photodegradation rate but did not affect the release rate. All ATRA-loaded NLC formulations exhibited the photoprotective property. The cytotoxicity results showed that all ATRA-loaded NLC had higher cytotoxicity than the free drug and HL-60 cells were more sensitive to ATRA than HepG2 cells.