Vicari Luisa, Musumeci Teresa, Giannone Ignazio, Adamo Luana, Conticello Concetta, De Maria Ruggero, Pignatello Rosario, Puglisi Giovanni, Gulisano Massimo
Dipartimento di Oncologia Sperimentale, Istituto Oncologico del Mediterraneo, Viagrande (CT), Italy.
BMC Cancer. 2008 Jul 25;8:212. doi: 10.1186/1471-2407-8-212.
PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor EL (polyethoxylated castor oil) and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration.
In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC.
NS loaded with 3% PTX (w/w) had a mean size < 250 nm and a polydispersity index of 0.4 after freeze-drying with 0.5% HP-Cyd as cryoprotector. PTX encapsulation efficiency was 30% and NS showed a prolonged drug release in vitro. An increase of the cytotoxic effect of PTX-NS was observed with respect to free PTX in all cell lines tested.
These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.
由于紫杉醇（PTX）对实体瘤和几种血液系统癌症具有高效性，它是肿瘤学中使用最广泛的药物之一。PTX以含有1:1聚氧乙烯蓖麻油（Cremophor EL）和乙醇的制剂形式给药，这些成分常导致毒性作用。将其封装在胶体递送系统中可改善对癌细胞的靶向性，减少给药剂量和频率。
本文将PTX负载于聚乳酸-羟基乙酸共聚物纳米粒（PLGA NS）中。在体外评估了PTX-NS对培养的甲状腺癌、乳腺癌和膀胱癌细胞系的活性。通过MTS法评估细胞生长，使用香豆素-6标记的纳米粒进行细胞内纳米粒摄取实验，并通过高效液相色谱法测量细胞内PTX的量。
以0.5%羟丙基-β-环糊精（HP-Cyd）作为冷冻保护剂冻干后，负载3%（w/w）PTX的纳米粒平均粒径<250 nm，多分散指数为0.4。PTX的包封率为30%，纳米粒在体外显示出药物的缓释。在所有测试的细胞系中，观察到PTX-NS相对于游离PTX的细胞毒性作用增强。
这些发现表明，PTX-NS更大的生物学效应可能归因于细胞内纳米粒摄取和细胞积累研究所示的药物在细胞内的更高摄取。
