聚乳酸载药纳米微粒制备及其释药效能

Preparation and Release Efficiency of Polylactic Acid Nanoparticle

背景与目的:医用纳米微粒作为药物传递和控释的载体,是一种新型的控释体系。它与微米粒子的主要区别是超微小体积,能穿过组织间隙并被细胞摄取,可通过毛细血管壁和血脑屏障,因而作为一种新的控释体系而被广泛研究。本研究拟制备聚乳酸纳米微粒,并对其表面形貌、粒径分布、微粒结构、表面元素、体外释放等微粒性能进行应用评估。方法:以可溶性聚乳酸为载体,5鄄氟尿嘧啶(5鄄fluorouracil,5鄄FU)为模型药物,采用超声乳化法制备聚乳酸载纳米微粒,通过电子显微镜观察纳米粒外形结构,用X射线光电能谱仪(X鄄rayphotoelectronspectroscopy,XPS)测定纳米微粒表面元素,用紫外分光光度计测纳米粒载药量和包封率,并测定体外释放量。结果:聚乳酸载纳米微粒呈规则球形,平均粒径(191±17)nm,载药量为15.2%,包封率为45.6%。体外释放实验表明纳米微粒具有缓释特性,在模拟体液中,10天的累积释药达94.27%。结论:以聚乳酸纳米微粒作为5鄄FU载体,可改变5鄄FU在体内的药代动力学行为,具有缓释作用,可制备为静脉用药,延长药物在体内的循环时间,发挥更好的抗肿瘤效应。

BACKGROUND ＆ OBJECTIVE： As a new drug delivery carrier, medical nanoparticle （NP） appears to be very promising and are widely studied. Compare with microparticle, nanoparticle possesses several advantages, such as ultramicroscopic size, could be ingested by the cells after crossing the tissue matrix, and can penetrate the arterial wall and cross the blood-brain barrier. This study was to prepare polylactic acid （PLA）nanoparticle, and observe its morphology, diameter, structure, surface elements, and ability of in vitro drug release. METHODS- The biodegradable PLA was used as the carrier, and 5-fluorouracil （5-FU） was used as the model drug. 5-FU-PLA nanoparticle （5-FU-PLA-NP） was prepared by matrix and ultrasound emulsification. Morphology of 5-FU-PLA-NP was observed under scanning electron microscope; its surface elements were detected by X ray photoelectron spectroscopy; its drug loading （DL）, embeding ratio（ER）, and ability of in vitro drug release were assessed by ultraviolet spectroscopy. RESULTS： The nanoparticle was uniformly spherical with average diameter of （191 ＋17） nm, DL of 15.2%, and ER of 45.6%. The nanoparticle showed sustained release character in the experiment of in vitro drug release, the cumulative drug release rate in analog body fluid was 94.3% at the 10th day. CONCLUSION： PLA-NP may serve as a carrier of 5-FU, and can change the pharmacokinetics of 5-FU, slower down drug release; 5-FU-PLA-NP can be prepared as intravenous injection, and may prolong the in vivo circulation time of 5-FU, so as to play more efficient antitumor effects.