Haloperidol-loaded PLGA nanoparticles: Systematic study of particle size and drug content
Haloperidol-loaded PLGA nanoparticles: Systematic study of particle size and drug content
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DOI：
10.1016/j.ijpharm.2006.11.061
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发表时间：
2007-05-24
影响因子：
5.8
通讯作者：
Winey, Karen I.
中科院分区：
文献类型：
--
作者：
Budhian, Avinash;Siegel, Steven J.;Winey, Karen I.
我们采用两种乳化-溶剂挥发法：均质法和超声法制备了氟哌啶醇聚乳酸/聚乳酸纳米粒。我们已经确定了五个独立的工艺参数和两个材料特性如何控制颗粒大小和药物含量。根据广泛适用于载药聚合物纳米颗粒生产的基本科学原理，讨论了工艺和材料参数之间的相互依赖关系以及随后的纳米颗粒特性。这种水平的理解应该会加快设计制造新药-PLGA纳米粒的方案的步伐。结果表明，氟哌啶醇PLGA/聚乳酸纳米粒的粒径受能量传递到有机相的剪切力的大小有效控制，而剪切力的大小与能量类型、水相体积和有机溶剂中聚合物浓度等参数密切相关。在制备的溶剂挥发阶段，通过减少药物从有机相到水相的扩散和通过增加药物与聚合物的相互作用来控制这些纳米粒子的药物含量。较大的粒径、较高的聚合物浓度和聚合物相对分子质量，以及通过调节pH降低药物在水相中的溶解度等显著抑制药物的扩散。特定的药物-聚合物相互作用是通过优化丙交酯与乙交酯的比率(L：G比率)并包括特定的聚合物端基来实现的。经优化后，载药PLGA/聚乳酸纳米粒的氟哌啶醇含量高达2.5%。(C)2006爱思唯尔B.V.保留所有权利。
We have produced haloperidol-loaded PLGA/PLA nanoparticles by using two emulsification-solvent evaporation methods: homogenization and sonication. We have established how five independent processing parameters and two materials characteristics control the particle size and drug content. The interdependencies between processing and materials parameters and the subsequent nanoparticle characteristics are discussed in terms of underlying scientific principles that are broadly applicable to the production of drug-loaded polymer nanoparticles. This level of understanding should quicken the pace of designing protocols for making new drug-PLGA nanoparticles. It was determined that the particle size of haloperidol-loaded PLGA/PLA nanoparticles is effectively controlled by the amount of shear stress transferred from the energy source to the organic phase, which is strongly correlated to the following parameters: type of applied energy, aqueous phase volume, and polymer concentration in the organic solvent. The drug content of these nanoparticles is controlled by reducing the diffusion of the drug from the organic to the aqueous phase during the solvent evaporation stage of the preparation and by increasing the drug-polymer interactions. The following significantly inhibit drug diffusion: large particle size, higher polymer concentration and polymer molecular weight, and reducing the drug solubility in the aqueous phase by adjusting the pH. Specific drug-polymer interactions are engineered by optimizing the lactide to glycolide ratio (L:G ratio) and including specific polymer end groups. When optimized, the drug-loaded PLGA/PLA nanoparticles contain as much as 2.5% haloperidol. (C) 2006 Elsevier B.V. All rights reserved.