Laboratory of Nanomedicine, Institute of Life Sciences, Nalco Square, Chandrasekarpur, Bhubaneswar, Orissa, India.
Biomaterials. 2010 Dec;31(35):9340-56. doi: 10.1016/j.biomaterials.2010.08.010. Epub 2010 Sep 20.
Gemcitabine [2', 2'-difluoro-2'-deoxycytidine (dFdC)] is a low molecular weight, deoxycytidine analog inhibiting cellular DNA synthesis. Currently, it is the frontline drug approved by Food and Drug Administration (FDA) for the treatment of pancreatic cancer. However, efforts to use gemcitabine as an anti-cancer agent have been limited by its short circulation time and rapid metabolism that reflects in low tumor uptake and intracellular action. Polymer-drug conjugates, in this regard have spawned an approach to improve the cytotoxicity efficiency and bioavailability of gemcitabine by chemical modification. The present study describes the synthesis of a water soluble formulation of PEGylated gemcitabine characterized by FT IR, (1)H NMR and RP-HPLC chromatography. The PEGylated gemcitabine has a prolonged circulation time in plasma as studied in an animal model. This eventually caused a marked improvement in the cytotoxicity and apoptosis-inducing activity in pancreatic cancer cell lines (MIA PaCa 2 and PANC 1). Hence, these findings demonstrate the PEGylated gemcitabine is a desirable approach for therapy by intravenous administration. Successful clinical application of this approach can significantly contribute to the treatment of pancreatic cancer.
吉西他滨[2', 2'-二氟-2'-脱氧胞苷（dFdC）]是一种低分子量的脱氧胞苷类似物，可抑制细胞 DNA 合成。目前，它是美国食品和药物管理局（FDA）批准用于治疗胰腺癌的一线药物。然而，由于其循环时间短和代谢迅速，导致肿瘤摄取和细胞内作用降低，限制了将吉西他滨用作抗癌药物的作用。在这方面，聚合物-药物偶联物产生了一种通过化学修饰来提高吉西他滨的细胞毒性效率和生物利用度的方法。本研究描述了一种水溶性聚乙二醇化吉西他滨制剂的合成，其特征在于傅里叶变换红外光谱（FTIR）、（1）H 核磁共振（NMR）和反相高效液相色谱（RP-HPLC）分析。在动物模型中研究表明，聚乙二醇化吉西他滨在血浆中的循环时间延长。这最终导致胰腺癌细胞系（MIA PaCa 2 和 PANC 1）的细胞毒性和诱导细胞凋亡活性显著改善。因此，这些发现表明聚乙二醇化吉西他滨是通过静脉给药治疗的一种理想方法。这种方法的成功临床应用将为治疗胰腺癌做出重大贡献。
