Vanslambrouck Stéphanie, Riva Raphaël, Ucakar Bernard, Préat Véronique, Gagliardi Mick, Molin Daniel G M, Lecomte Philippe, Jérôme Christine
Center for Education and Research on Macromolecules (CERM), CESAM Research-Unit, University of Liège, Allée du 6 août 13, B6a, Sart-Tilman, 4000 Liège, Belgium.
Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute, Université Catholique de Louvain, Avenue Mounier, 73, B1.73.12, 1200 Brussels, Belgium.
Molecules. 2021 Mar 20;26(6):1750. doi: 10.3390/molecules26061750.
Poly(ethylene glycol)--polyphosphoester (PEG--PPE) block copolymer nanoparticles are promising carriers for poorly water soluble drugs. To enhance the drug loading capacity and efficiency of such micelles, a strategy was investigated for increasing the lipophilicity of the PPE block of these PEG--PPE amphiphilic copolymers. A PEG--PPE copolymer bearing pendant vinyl groups along the PPE block was synthesized and then modified by thiol-ene click reaction with thiols bearing either a long linear alkyl chain (dodecyl) or a tocopherol moiety. Ketoconazole was used as model for hydrophobic drugs. Comparison of the drug loading with PEG--PPE bearing shorter pendant groups is reported evidencing the key role of the structure of the pendant group on the PPE backbone. Finally, a first evidence of the biocompatibility of these novel PEG--PPE copolymers was achieved by performing cytotoxicity tests. The PEG--PPE derived by tocopherol was evidenced as particularly promising as delivery system of poorly water-soluble drugs.
聚乙二醇-聚磷酸酯（PEG-PPE）嵌段共聚物纳米粒是用于难溶性药物的有前景的载体。为了提高此类胶束的载药量和效率，研究了一种提高这些PEG-PPE两亲共聚物PPE嵌段亲脂性的策略。合成了一种沿PPE嵌段带有侧链乙烯基的PEG-PPE共聚物，然后通过硫醇-烯点击反应与带有长线性烷基链（十二烷基）或生育酚部分的硫醇进行修饰。酮康唑用作疏水药物的模型。报道了与带有较短侧链基团的PEG-PPE的载药量比较，证明了PPE主链上侧链基团结构的关键作用。最后，通过进行细胞毒性试验首次证明了这些新型PEG-PPE共聚物的生物相容性。由生育酚衍生的PEG-PPE被证明作为难溶性药物的递送系统特别有前景。
