Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
Research Centre Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria; Institute of Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010 Graz, Austria.
Int J Pharm. 2020 Apr 30;580:119199. doi: 10.1016/j.ijpharm.2020.119199. Epub 2020 Mar 5.
Previously, we reported on the surfactant cetylpyridinium chloride (CPC) as a crosslinker of alginate for the formation of stable polyelectrolyte-surfactant-complex nanoparticles. Here, we evaluate this system for increased solubility of a poorly soluble drug. The aim was to use CPC for solubilisation of ibuprofen and to use the micellar associates formed for alginate complexation and nanoparticle formation. We acquired deeper insights into the entropy led interactions between alginate, CPC and ibuprofen. Stable nanoparticles were formed across limited surfactant-to-polyelectrolyte molar ratios, with ~150 nm hydrodynamic diameter, monodispersed distribution, and negative zeta potential (-40 mV), with 34% ibuprofen loading. Their structure was obtained using small-angle X-ray scattering, which indicated disordered micellar associates when ibuprofen was incorporated. This resulted in nanoparticles with a complex nanostructured composition, as shown by transmission electron microscopy. Drug release from ibuprofen-cetylpyridinium-alginate nanoparticles was not hindered by alginate, and was similar to the release kinetics from ibuprofen-CPC solubilisates. These innovative carriers developed as polyelectrolyte-surfactant complexes can be used for solubilisation of poorly soluble drugs, where the surfactant simultaneously increases the solubility of the drug at concentrations below its critical micellar concentration and crosslinks the polyelectrolyte to form nanoparticles.
先前，我们曾报道过表面活性剂十六烷基吡啶氯（CPC）作为海藻酸盐的交联剂，用于形成稳定的聚电解质-表面活性剂-复合物纳米颗粒。在这里，我们评估了该系统在提高难溶性药物溶解度方面的应用。目的是使用 CPC 增溶布洛芬，并利用形成的胶束缔合物进行海藻酸盐复合和纳米颗粒形成。我们深入了解了海藻酸盐、CPC 和布洛芬之间的熵驱动相互作用。在有限的表面活性剂-聚电解质摩尔比范围内形成了稳定的纳米颗粒，具有约 150nm 的水动力直径、单分散分布和负的 zeta 电位（-40mV），载药量为 34%。使用小角 X 射线散射获得了它们的结构，结果表明当布洛芬被掺入时，形成了无序的胶束缔合物。这导致了具有复杂纳米结构组成的纳米颗粒，如透射电子显微镜所示。布洛芬-十六烷基吡啶-海藻酸盐纳米颗粒中的药物释放不受海藻酸盐的阻碍，与布洛芬-CPC 增溶物的释放动力学相似。这些作为聚电解质-表面活性剂复合物开发的创新载体可用于增溶难溶性药物，其中表面活性剂在低于其临界胶束浓度的浓度下同时增加药物的溶解度，并交联聚电解质形成纳米颗粒。
