Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstr. 10, 07743 Jena, Germany.
Jena Center for Soft Matter, Friedrich Schiller University Jena, Philosophenweg 7, 07743 Jena, Germany.
Anal Chem. 2023 Jan 17;95(2):565-569. doi: 10.1021/acs.analchem.2c04277. Epub 2022 Dec 22.
Multifunctional nanoparticle (NP) formulations for medical purposes have already found their way toward envisaged translation. A persistent challenge of those systems is, next to NP size analysis, the compositional analysis of the NPs with the polymer as the matrix component and the encapsulated drug, particularly in a quantitative manner. Herein, we report the formulation of poly(lactic--glycolic acid) (PLGA) NPs by nanoprecipitation and the analysis of their integrity and size by dynamic light scattering (DLS) and scanning electron microscopy (SEM). Those NPs feature a variety of encapsulated drugs including the well-known ibuprofen (Ibu) as well as dexamethasone (Dex) and dexamethasone acetate (DexAce), with the latter being of potential interest for clinical treatment of SARS-CoV-2 patients. All those dissolved formulation compositions have been subjected to liquid chromatography on reversed-phase silica monolithic columns, allowing to quantitatively assess amounts of small molecule drug and NP constituting PLGA polymer in a single run. The chromatographically resolved hydrophobicity differences of the drugs correlated with their formulation loading and were clearly separated from the PLGA matrix polymer with high resolution. Our study identifies the viability of reversed-phase monolithic silica in the chromatography of both small drug molecules and particularly pharmapolymers in a repeatable and simultaneous fashion, and can provide a valuable strategy for analysis of diverse precursor polymer systems and drug components in multifunctional drug formulations.
多功能纳米粒子（NP）制剂已经在医学用途方面得到了广泛的应用。这些系统的一个持续挑战是，除了 NP 大小分析之外，还需要对聚合物基质成分和封装药物的 NPs 进行组成分析，特别是定量分析。在此，我们报告了通过纳米沉淀法制备聚（乳酸-乙醇酸）（PLGA）NP，并通过动态光散射（DLS）和扫描电子显微镜（SEM）分析其完整性和大小。这些 NPs 包含多种封装药物，包括众所周知的布洛芬（Ibu）以及地塞米松（Dex）和地塞米松醋酸酯（DexAce），后者对于 SARS-CoV-2 患者的临床治疗具有潜在的意义。所有这些溶解制剂成分都经过反相硅胶整体柱的液相色谱分析，允许在单次运行中定量评估小分子药物和构成 PLGA 聚合物的 NP 的含量。药物的色谱分离疏水性差异与其制剂负载相关，并与 PLGA 基质聚合物高度分离，具有高分辨率。我们的研究表明，反相硅胶整体柱在小分子药物和特别是药用聚合物的色谱分析中具有可行性，可以为多功能药物制剂中各种前体聚合物系统和药物成分的分析提供有价值的策略。
