Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Campus Universitario S. Venuta - Building of BioSciences, Viale Europa, I-88100 Germaneto (CZ), Italy.
J Control Release. 2010 Jun 1;144(2):144-50. doi: 10.1016/j.jconrel.2010.02.021. Epub 2010 Feb 22.
The systemic efficacy of the chemotherapeutic agents presently used to treat solid tumors is limited by their low therapeutic index. Previously, our research group improved the in vitro antitumoral activity of gemcitabine, an anticancer agent rapidly deaminated to the inactive metabolite 2',2'-difluorodeoxyuridine, entrapping it into unilamellar pegylated liposomes made up of 1,2-dipalmitoyl-snglycero-3-phosphocholine monohydrate/cholesterol/N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (6:3:1 molar ratio). In this work, we investigated the in vivo efficiency of the gemcitabine liposomal formulation (5mg/kg) with respect to the antitumoral commercial product GEMZAR (50mg/kg) on an anaplastic thyroid carcinoma xenograft model obtaining similar effects in terms of inhibition of tumor mass proliferation after 4weeks of treatment. The investigation of the carrier biodistribution and the drug pharmacokinetic profile furnished the rationalization of the efficacy of the vesicular system containing the active compound 10-fold less concentrated; in fact, liposomes promoted the concentration of the drug inside the tumor and they increased its plasmatic half-life. In addition, no signs of blood toxicity were observed when vesicular devices of effective doses of the drug were used.
目前用于治疗实体瘤的化疗药物的全身疗效受到其治疗指数低的限制。以前，我们的研究小组通过将阿糖胞苷（一种抗癌药物，迅速脱氨为无活性代谢物 2'，2'-二氟脱氧尿苷）包封在由 1,2-二棕榈酰-snglycero-3-磷酸胆碱单水合物/胆固醇/N-（羰基-甲氧基聚乙二醇-2000）-1,2-二硬脂酰-snglycero-3-磷酸乙醇胺（6:3:1 摩尔比）组成的单室 PEG 化脂质体中来提高其体外抗肿瘤活性。在这项工作中，我们研究了阿糖胞苷脂质体制剂（5mg/kg）与抗肿瘤商业产品 Gemzar（50mg/kg）在间变性甲状腺癌异种移植模型中的体内效率，在治疗 4 周后，在抑制肿瘤质量增殖方面取得了相似的效果。载体生物分布和药物药代动力学特征的研究为含有活性化合物的囊泡系统的功效提供了合理化解释，因为该系统中药物的浓度低 10 倍；事实上，脂质体促进了药物在肿瘤内的浓度，并增加了其血浆半衰期。此外，当使用有效剂量的囊泡药物时，没有观察到血液毒性的迹象。
