Xiangya School of Medicine, Central South University, Changsha, Hunan Province, People's Republic of China.
Int J Nanomedicine. 2010 Nov 24;5:1039-48. doi: 10.2147/IJN.S14753.
Endostar, a novel recombinant human endostatin, which was approved by the Chinese State Food and Drug Administration in 2005, has a broad spectrum of activity against solid tumors. In this study, we aimed to determine whether the anticancer effect of Endostar is increased by using a nanocarrier system. It is expected that the prolonged circulation of endostar will improve its anticancer activity. Endostar-loaded nanoparticles were prepared to improve controlled release of the drug in mice and rabbits, as well as its anticancer effects in mice with colon cancer. A protein release system could be exploited to act as a drug carrier. Nanoparticles were formulated from poly (ethylene glycol) modified poly (DL-lactide-co-glycolide) (PEG-PLGA) by a double emulsion technique. Physical and release characteristics of endostar-loaded nanoparticles in vitro were evaluated by transmission electron microscopy (TEM), photon correlation spectroscopy (PCS), and micro bicinchoninic acid protein assay. The pharmacokinetic parameters of endostar nanoparticles in rabbit and mice plasma were measured by enzyme-linked immunosorbent assay. Western blot was used to detect endostatin in different tissues. To study the effects of endostar-loaded nanoparticles in vivo, nude mice in which tumor cells HT-29 were implanted, were subsequently treated with endostar or endostar-loaded PEG-PLGA nanoparticles. Using TEM and PCS, endostar-loaded PEG-PLGA nanoparticles were found to have a spherical core-shell structure with a diameter of 169.56 ± 35.03 nm. Drug-loading capacity was 8.22% ± 2.35% and drug encapsulation was 80.17% ± 7.83%. Compared with endostar, endostar-loaded PEG-PLGA nanoparticles had a longer elimination half-life and lower peak concentration, caused slower growth of tumor cell xenografts, and prolonged tumor doubling times. The nanoparticles changed the pharmacokinetic characteristics of endostar in mice and rabbits, thereby reinforcing anticancer activity. In conclusion, PEG-PLGA nanoparticles are a feasible carrier for endostar. Endostar-loaded PEG-PLGA nanoparticles seem to have a better anticancer effect than conventional endostar. We believe that PEG-PLGA nanoparticles are an effective carrier for protein medicines.
恩度，一种新型重组人血管内皮抑制素，于 2005 年被中国国家食品药品监督管理局批准上市，对实体肿瘤具有广谱的活性。在本研究中，我们旨在确定使用纳米载体系统是否能增强恩度的抗癌作用。预计恩度的循环时间延长将提高其抗癌活性。我们制备了载恩度纳米粒，以改善药物在小鼠和兔体内的控释，并提高载恩度纳米粒在结肠癌小鼠中的抗癌作用。蛋白质释放系统可以被开发为药物载体。纳米粒由聚乙二醇（PEG）修饰的聚（DL-丙交酯-乙交酯）（PEG-PLGA）通过双乳液技术制备。通过透射电子显微镜（TEM）、光相关光谱（PCS）和微比色法蛋白分析评估载恩度纳米粒的体外药物释放特性。通过酶联免疫吸附试验（ELISA）测定兔和小鼠血浆中载恩度纳米粒的药代动力学参数。Western blot 用于检测不同组织中的血管内皮抑制素。为了研究载恩度纳米粒在体内的作用，将 HT-29 肿瘤细胞植入裸鼠，随后用恩度或载恩度的 PEG-PLGA 纳米粒进行治疗。通过 TEM 和 PCS 发现，载恩度的 PEG-PLGA 纳米粒具有 169.56 ± 35.03nm 的球形核壳结构。载药量为 8.22% ± 2.35%，包封率为 80.17% ± 7.83%。与恩度相比，载恩度的 PEG-PLGA 纳米粒具有更长的消除半衰期和更低的峰浓度，导致肿瘤细胞异种移植物生长缓慢，肿瘤倍增时间延长。纳米粒改变了恩度在小鼠和兔体内的药代动力学特征，从而增强了抗癌活性。总之，PEG-PLGA 纳米粒是恩度的一种可行载体。载恩度的 PEG-PLGA 纳米粒似乎比常规恩度具有更好的抗癌效果。我们认为，PEG-PLGA 纳米粒是蛋白质药物的有效载体。
