Faculty of Biotechnology and Food Engineering, Technion, Haifa 32000, Israel.
Faculty of Biotechnology and Food Engineering, Technion, Haifa 32000, Israel.
J Control Release. 2017 Jul 10;257:76-83. doi: 10.1016/j.jconrel.2016.09.025. Epub 2016 Sep 24.
Camptothecin (CPT) is a naturally occurring cytotoxic alkaloid having a broad spectrum of antitumor activity. Unfortunately, it has low bioavailability and encapsulation efficiency, limiting its clinical use. We report on our efforts to develop a novel drug delivery prototype composed of a short, star hydrophilic polyethylene glycol (PEG) backbone and hydrophobic CPT (PEG-CPT). The amphiphilic bio-conjugate self-assembles in water into stable spherical nano-particles with a mean diameter of 200nm and CPT substitution percentage of 27%w/w. CPT is released in a sustained release profile without burst effect. In addition, PEG-CPT nano-particles are able to load a co-drug, water soluble or non-water soluble doxorubicin and release them simultaneously with the free CPT. The biological evaluation of PEG-CPT against HeLa cells showed improved cellular uptake and enhanced cytotoxicity compared to free CPT. Thus, in this approach CPT acts in two ways: As the hydrophobic segment that enables self-assembly in water and as a potent anticancer agent. This concept of combining hydrophobic drugs and short star polymers shows great potential for efficient delivery of hydrophobic chemotrophic drugs as well as for drugs with inherent stability and pharmacokinetic barriers.
喜树碱（CPT）是一种天然存在的细胞毒性生物碱，具有广谱的抗肿瘤活性。不幸的是，它的生物利用度和包封效率都很低，限制了它的临床应用。我们报告了我们开发一种由短的星形亲水性聚乙二醇（PEG）主链和疏水性 CPT（PEG-CPT）组成的新型药物传递原型的努力。两亲性生物缀合物在水中自组装成稳定的球形纳米颗粒，平均直径为 200nm，CPT 取代度为 27%w/w。CPT 以无突释效应的持续释放方式释放。此外，PEG-CPT 纳米颗粒能够负载共药物，水溶性或非水溶性阿霉素，并与游离 CPT 同时释放。与游离 CPT 相比，PEG-CPT 对 HeLa 细胞的生物学评价显示出改善的细胞摄取和增强的细胞毒性。因此，在这种方法中，CPT 以两种方式发挥作用：作为在水中能够自组装的疏水性部分，以及作为一种有效的抗癌剂。这种将疏水性药物与短星形聚合物结合的概念显示出高效传递疏水性趋化药物以及具有固有稳定性和药代动力学障碍的药物的巨大潜力。
