IBMM, University of Montpellier, CNRS, ENSCM, Montpellier, France.
IBMM, University of Montpellier, CNRS, ENSCM, Montpellier, France.
J Chromatogr A. 2024 Mar 15;1718:464719. doi: 10.1016/j.chroma.2024.464719. Epub 2024 Feb 5.
Dendrigraft poly(L-lysine) (DGL) constitutes a promising dendritic-like drug vehicle with high biocompatibility and straightforward access via ring-opening polymerization of N-carboxyanhydride in water. The characterization of the different generations of DGL is however challenging due to their heterogeneity in molar mass and branching ratio. In this work, free solution capillary electrophoresis was used to perform selective separation of the three first generations of DGL, and optimized conditions were developed to maximize inter-generation resolution. To reduce solute adsorption on the capillary wall, successive multiple ionic polymer layer coatings terminated with a polycation were deposited onto the inner wall surface. PEGylated polycation was also used as the last layer for the control of the electroosmotic flow (EOF), depending on the PEGylation degree and the methyl-polyethylene glycol (mPEG) chain length. 1 kDa mPEG chains and low grafting densities were found to be the best experimental conditions for a fine tuning of the EOF leading to high peak resolution. Molar mass polydispersity and polydispersity in effective electrophoretic mobility were successfully determined for the three first generations of DGL.
树枝状聚赖氨酸（DGL）是一种很有前途的树枝状药物载体，具有生物相容性高的特点，并且可以通过 N-羧基酸酐在水中的开环聚合反应很容易地得到。然而，由于其分子量和支化比的异质性，不同代数的 DGL 的特性分析具有一定挑战性。在这项工作中，我们使用自由溶液毛细管电泳对 DGL 的前三代进行选择性分离，并优化了条件以最大限度地提高代际分辨率。为了减少溶质在毛细管壁上的吸附，我们采用了连续的多层离子聚合物涂层，其末端是聚阳离子。还使用了聚乙二醇化聚阳离子作为最后一层，以控制电渗流（EOF），具体取决于聚乙二醇化程度和甲基-聚乙二醇（mPEG）链长。实验结果表明，1 kDa 的 mPEG 链和低接枝密度是精细调节 EOF 的最佳实验条件，可实现高的峰分辨率。我们成功地确定了 DGL 的前三代的分子量多分散性和有效电泳迁移率的多分散性。
