A novel size-tunable nanocarrier system for targeted anticancer drug delivery.
A novel size-tunable nanocarrier system for targeted anticancer drug delivery.
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DOI：
10.1016/j.jconrel.2010.02.027
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发表时间：
2010-06-15
期刊：
影响因子：
--
通讯作者：
Lam KS
中科院分区：
文献类型：
--
作者：
Li Y;Xiao K;Luo J;Lee J;Pan S;Lam KS
我们开发了一种基于胶束的纳米载体给药系统，该胶束由一类新的定义明确的线性聚乙二醇化的两臂胆酸低聚物在水溶液中形成。通过改变线性PEG链的长度和胆酸低聚物的构型，可以容易地微调两亲聚合物和所得胶束的物理化学性质。这些参数包括粒径、临界胶束浓度和载药量。高水平的疏水性抗癌药物如PTX、依托泊苷和SN-38可以容易地装载到这样的纳米载体中。紫杉醇（PTX）的纳米载体的负载能力是非常高的（12.0 mg/mL），这相当于胶束的总质量的37.5%（w/w）。当储存在牛血清白蛋白溶液或狗血浆中时，装载PTX的纳米载体比Abraxane®（PTX/人血清白蛋白纳米聚集体）稳定得多。PTX从胶束中的释放曲线是无爆发的，并持续7天。在持续药物暴露的情况下，负载PTX的纳米载体在体外针对卵巢癌细胞系的抗肿瘤活性类似于Taxol®（溶于Cremophor EL和乙醇中的PTX制剂）或Abraxane®。近红外荧光（NIRF）成像显示，这些新的胶束靶向药物输送到肿瘤部位的荷卵巢癌裸鼠移植瘤。此外，在卵巢癌异种移植物模型中，在等效PTX剂量下，与Taxol®相比，负载PTX的纳米载体表现出上级抗肿瘤功效。
We have developed a nanocarrier drug-delivery system based on micelles formed by a new class of well-defined linear PEGylated two-arm oligomer of cholic acids in aqueous solution. By varying the length of the linear PEG chains and the configuration of cholic acid oligomer, one can easily fine-tune the physicochemical properties of the amphiphilic polymers and the resulting micelles. These include particle size, critical micelle concentration, and drug loading capacity. High level of hydrophobic anticancer drugs such as PTX, etoposide and SN-38 can be readily loaded into such nanocarriers. The loading capacity of the nanocarrier for PTX (PTX) is extremely high (12.0 mg/mL), which is equivalent to 37.5% (w/w) of the total mass of the micelle. PTX-loaded nanocarriers are much more stable than Abraxane® (PTX/human serum albumin nanoaggregate) when stored in bovine serum albumin solution or dog plasma. PTX release profile from the micelles is burst-free and sustained over a period of seven days. The anti-tumor activity of PTX-loaded nanocarriers against ovarian cancer cell line in vitro, with continuous drug exposure, is similar to Taxol® (formulation of PTX dissolved in Cremophor EL and ethanol) or Abraxane®. Targeted drug delivery to tumor site with these novel micelles was demonstrated by near infrared fluorescence (NIRF) imaging in nude mice bearing ovarian cancer xenograft. Furthermore, PTX-loaded nanocarriers demonstrated superior anti-tumor efficacy compared to Taxol® at equivalent PTX dose in ovarian cancer xenograft model.
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