Improved cytotoxicity of paclitaxel loaded in nanosized lipid carriers by intracellular delivery
Improved cytotoxicity of paclitaxel loaded in nanosized lipid carriers by intracellular delivery
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通过细胞内递送改善纳米脂质载体中负载的紫杉醇的细胞毒性
DOI：
10.1007/s11051-014-2852-x
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发表时间：
2015-01-11
影响因子：
2.5
通讯作者：
Hu, Fuqiang
中科院分区：
文献类型：
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作者：
Miao, Jing;Du, Yongzhong;Hu, Fuqiang
纳米脂质载体(NLC)可以改善固体脂质纳米粒(SLN)的极限载药量和储存过程中的药物释放，调整固体脂质纳米粒的释药规律。本研究以单甘酯为固体脂质，油酸为液体脂基质，采用溶剂扩散法制备了紫杉醇(PTX)纳米粒。不同油酸含量的空白纳米粒(粒径范围为89.5±77.4~160.2±34.6 nm)比空白纳米粒(尺寸为272.7±43.6 nm)的尺寸小，而载药纳米粒(粒径范围为481.3±29.8~561.7±38.3 nm)的尺寸稍大，载药容量较大，体外释药速度较快。含0、5、10、20wt%OA的PTX载药NLC的半数细胞生长抑制率(IC50)分别为0.92g±0.06、0.69g±0.04、0.25g±0.02和0.12g±0.02µg/mL−1，而TaxolTM的IC50值为1.72±0.09g/mLOF1。为了分析细胞药物效应，我们考察了细胞对荧光NLC的摄取量和细胞内药物浓度。在NLC负载的固体脂质基质中可以促进细胞摄取和PTX的转运，因此PTX的细胞毒性可以增强，并且随着NLC中OA含量的增加而进一步增强。
Nanosized lipid carriers (NLC) can improve the limited drug-loading (DL) capacity and drug expulsion during storage, and adjust the drug release profile of solid lipid nanoparticles (SLN). In this study, Paclitaxel (PTX)-loaded NLC were prepared by solvent diffusion method using monostearin as solid lipid and oleic acid (OA) as liquid lipid matrix. The blank NLC with different OA content (the size range was from 89.5 ± 7.4 to 160.2 ± 34.6 nm) showed smaller size than the blank SLN (the size was 272.7 ± 43.6 nm), while the PTX-loaded NLC (the size range was from 481.3 ± 29.8 to 561.7 ± 38.3 nm) showed little bigger size, higher DL capacity, and faster drug in vitro release rate comparing with SLN (the size was 437.3 ± 68.2 nm). The 50 % cellular growth inhibitions (IC50) of PTX-loaded NLC with 0, 5, 10, and 20 wt % OA were 0.92 ± 0.06, 0.69 ± 0.04, 0.25 ± 0.02, and 0.12 ± 0.02 µg mL−1, respectively, while the IC50of TaxolTMwas 1.72 ± 0.09 µg mL−1. For analyzing cellular drug effect, cellular uptakes of fluorescent NLC and intracellular drug concentration were investigated. As the incorporation of OA into solid lipid matrix could accelerate both the cellular uptake and the PTX delivery, loaded by NLC, the cytotoxicity of PTX could be enhanced, and further enhanced by increasing OA content in NLC.