Lamprecht A, Ubrich N, Hombreiro Pérez M, Lehr C, Hoffman M, Maincent P
Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté de Pharmacie, BP 403, 5 rue A. Lebrun, 54001, Nancy Cedex, France.
Int J Pharm. 1999 Jul 5;184(1):97-105. doi: 10.1016/s0378-5173(99)00107-6.
The aim of the present work was to investigate the preparation of nanoparticles (NP) as potential drug carriers for proteins. The hydrophilic protein bovine serum albumin (BSA) was chosen as the model drug to be incorporated within NP. Owing to the high solubility of the protein in water, the double emulsion technique has been chosen as one of the most appropriate method. In order to reach submicron size we used a microfluidizer as a homogenization device with a view to obtaining NP with a very high grade of monodispersity. Two different biodegradable polymers, poly[D, L-lactic-co-glycolic acid] 50/50 (PLGA) and poly[epsilon-caprolactone] (PCL) has been used for the preparation of the NP. The drug loading has been optimized by varying the concentration of the protein in the inner aqueous phase, the polymer in the organic phase, the surfactant in the external aqueous phase, as well as the volume of the external aqueous phase. The BSA encapsulation efficiency was high (>80%) and release profiles were characterized by a substantial initial burst release for both PLGA and PCL NP. A higher release was obtained at the end of the dissolution study for PLGA NP (92%) compared with PCL NP (72%).
本研究的目的是研究纳米颗粒(NP)作为蛋白质潜在药物载体的制备方法。选择亲水性蛋白质牛血清白蛋白(BSA)作为模型药物纳入NP中。由于蛋白质在水中的高溶解度,双乳液技术被选为最合适的方法之一。为了达到亚微米尺寸,我们使用微流体化器作为均质化装置,以期获得具有非常高单分散性的NP。两种不同的可生物降解聚合物,聚[D,L-乳酸-共-乙醇酸] 50/50(PLGA)和聚[ε-己内酯](PCL)已用于制备NP。通过改变内水相中的蛋白质浓度、有机相中的聚合物浓度、外水相中的表面活性剂浓度以及外水相的体积,对药物负载进行了优化。BSA的包封效率很高(>80%),PLGA和PCL NP的释放曲线均以大量的初始突释为特征。在溶出度研究结束时,PLGA NP的释放率(92%)高于PCL NP(72%)。