Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles
Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles
复制标题
DOI：
10.1016/j.ejps.2004.09.011
复制
发表时间：
2005-01-01
影响因子：
4.6
通讯作者：
Doelker, E
中科院分区：
文献类型：
--
作者：
Bilati, U;Allémann, E;Doelker, E
本研究调查配方和工艺修改，以提高纳米沉淀技术的多功能性，特别是相对于亲水性药物（如蛋白质）的封装。更具体地说，主要目的是探索这种修饰对纳米颗粒尺寸的影响。改变纳米沉淀法的选定参数，如溶剂和非溶剂性质、溶剂/非溶剂体积比和聚合物浓度，以获得聚合物纳米载体。评估了这种改进方法的可行性，并对所得未负载纳米颗粒的尺寸和形状进行了表征。结果表明，平均粒径与所选非溶剂的类型密切相关。当使用醇时，最终平均尺寸按甲醇<乙醇<丙醇的顺序增加。添加到分散介质中的表面活性剂对于最终的悬浮液稳定化通常是不必要的。改变溶剂/非溶剂体积比也不是纳米颗粒形成及其最终特性的决定性因素，条件是最终混合物本身不会成为聚合物的溶剂。然而，溶剂中过高的聚合物浓度阻止了纳米颗粒的形成。通过选择合适的聚合物溶剂，可以同时使用聚乳酸（PLA）和聚（D，L-乳酸-羟基乙酸）共聚物（PLGA），并选择了一些具有不同介电常数的无毒溶剂。所获得的纳米颗粒的尺寸范围为约85 - 560 nm。然而，纳米颗粒回收步骤需要进一步改进，因为可以观察到导致絮凝的颗粒之间的桥。最后，所呈现的结果表明，纳米沉淀技术比以前认为的更通用和灵活，并且可以修改广泛的参数。(C)2004 Elsevier B.V.保留所有权利。
This study investigates formulation and process modifications to improve the versatility of the nanoprecipitation technique, particularly with respect to the encapsulation of hydrophilic drugs (e.g. proteins). More specifically, the principal objective was to explore the influence of such modifications on nanoparticle size. Selected parameters of the nanoprecipitation method, such as the solvent and the non-solvent nature, the solvent/non-solvent volume ratio and the polymer concentration, were varied so as to obtain polymeric nano-carriers. The feasibility of such a modified method was assessed and resulting unloaded nanoparticles were characterized with respect to their size and shape. It was shown that the mean particle size was closely dependent on the type of non-solvent selected. When alcohols were used, the final mean size increased in the sequence: methanol < ethanol < propanol. Surfactants added to the dispersing medium were usually unnecessary for final suspension stabilization. Changing the solvent/non-solvent volume ratio was also not a determinant factor for nanoparticle formation and their final characteristics, provided that the final mixture itself did not become a solvent for the polymer. A too high polymer concentration in the solvent, however, prevented nanoparticle formation. Both poly(lactic acid) (PLA) and poly(D,L-lactic-co-glycolic acid) (PLGA) could be used by accurately choosing the polymer solvent and in this respect, some non-toxic solvents with different dielectric constants were selected. The nanoparticles obtained ranged from about 85-560 nm in size. The nanoparticle recovery step however needs further improvements, since bridges between particles which cause flocculation Could be observed. Finally, the presented results demonstrate that the nanoprecipitation technique is more versatile and flexible than previously thought and that a wide range of parameters can be modified. (C) 2004 Elsevier B.V. All rights reserved.