Jiao Y Y, Ubrich N, Marchand-Arvier M, Vigneron C, Hoffman M, Maincent P
Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté de Pharmacie, Nancy, France.
Drug Deliv. 2001 Jul-Aug;8(3):135-41. doi: 10.1080/107175401316906892.
Nanoparticles of a highly soluble macromolecular drug, heparin, were formulated with two biodegradable polymers (poly-E-caprolactone [PCL] and poly (D, L-lactic-co-glycolic-acid) 50/50 [PLAGA]) and two nonbiodegradable positively charged polymers (Eudragit RS and RL) by the double emulsion and solvent evaporation method, using a high-pressure homogenization device. The encapsulation efficiency and heparin release profiles were studied as a function of the type of polymers employed (alone or in combination) and the concentration of heparin. Optimal encapsulation efficiency was observed when 5000 IU of heparin were incorporated in the first emulsion. High drug entrapment efficiency was observed in both Eudragit RS and RL nanoparticles (60% and 98%, respectively), compared with PLAGA and PCL nanoparticles (<14%). The use of the two types of Eudragit in combination with PCL and PLAGA increased the encapsulation efficiency compared with these two biodegradable polymers used alone; however, the in vitro drug release was not modified and remained low. On the other hand, the addition of esterase to the dissolution medium resulted in a significant increase in heparin release. The in vitro biological activity of released heparin, evaluated by measuring the anti-Xa activity by a colorimetric assay, was conserved after the encapsulation process.
采用双乳液溶剂蒸发法，利用高压均质装置，将高溶解性大分子药物肝素与两种可生物降解聚合物（聚-ε-己内酯[PCL]和聚（D，L-乳酸-共-乙醇酸）50/50[PLAGA]）以及两种不可生物降解的带正电荷聚合物（尤特奇RS和RL）制成纳米颗粒。研究了包封效率和肝素释放曲线与所用聚合物类型（单独或组合使用）以及肝素浓度的关系。当在第一乳液中加入5000国际单位肝素时，观察到最佳包封效率。与PLAGA和PCL纳米颗粒（<14%）相比，在尤特奇RS和RL纳米颗粒中均观察到较高的药物截留效率（分别为60%和98%）。与单独使用这两种可生物降解聚合物相比，将两种类型的尤特奇与PCL和PLAGA联合使用可提高包封效率；然而，体外药物释放未改变且仍然较低。另一方面，在溶出介质中加入酯酶导致肝素释放显著增加。通过比色法测量抗Xa活性评估，释放的肝素在包封过程后仍保留其体外生物活性。
