Wang Huimin, Ling Kanran, Hu Qingting, Ding Hanchen, Li Ran, Li Miao, Xu Si, Cao Yangyang
Research and Development Department, Hangzhou Ultra-Theranostics Biopharmaceuticals Technology Co., Ltd, Hangzhou, China.
Hangzhou No. 14 High School of Zhejiang Province, Hangzhou, China.
J Biomater Sci Polym Ed. 2025 Jun 25:1-12. doi: 10.1080/09205063.2025.2522744.
As surfactants, amphiphilic molecules form micelles in aqueous solution to load hydrophobic medicines to increase their solubility and absorbability. TPGS, i.e. VE-PEG conjugate, is a commonly used effective surfactant suffering immune effects in human bodies with reduced biocompatibility and stealth property. Among the potential alternatives of PEG, polysarcosine (pSar) is the most promising one due to its outstanding property and effectiveness. Herein, we propose two strategies to polymerize Sar-NPC, and to conjugate hydrophobic building blocks onto pSar. applies amino-group-containing lipids 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as initiators to produce DSPE-pSar and DOPE-pSar, respectively. changes chain end amino group of pSar to carboxyl group for esterification with the hydroxyl groups on vitamin E (VE) and 1,2-dimyristoyl-sn-glycerol (DMG) to produce VE-pSar and DMG-pSar. The degrees of polymerization of pSar blocks are designed to be 14, 25 and 28 precisely, and the CMC values of the amphiphilic products are between 0.28 and 5.63 µg/mL. VE-pSar samples have extremely strong ability to increase the solubility of paclitaxel (PTX), 30 times more than TPGS. It also exhibits high cytocompatibility and low hemolysis rate below 5%, much less than TPGS. The two preparations of pSar-containing surfactants are efficient and versatile, and the products have high probability to become a new generation of clinical hydrophobic medicine solubilizer.
作为表面活性剂，两亲性分子在水溶液中形成胶束以负载疏水性药物，从而提高其溶解度和吸收性。TPGS，即维生素E-聚乙二醇缀合物，是一种常用的有效表面活性剂，但在人体中会产生免疫效应，生物相容性和隐身性能降低。在聚乙二醇的潜在替代物中，聚肌氨酸（pSar）因其出色的性能和有效性而最具前景。在此，我们提出了两种策略来聚合Sar-NPC，并将疏水性结构单元连接到pSar上。一种方法是使用含氨基的脂质1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺（DSPE）和1,2-二油酰-sn-甘油-3-磷酸乙醇胺（DOPE）作为引发剂，分别制备DSPE-pSar和DOPE-pSar。另一种方法是将pSar的链端氨基转变为羧基，以便与维生素E（VE）和1,2-二肉豆蔻酰-sn-甘油（DMG）上的羟基进行酯化反应，从而制备VE-pSar和DMG-pSar。pSar嵌段的聚合度精确设计为14、25和28，两亲性产物的临界胶束浓度（CMC）值在0.28至5.63μg/mL之间。VE-pSar样品具有极强的增加紫杉醇（PTX）溶解度的能力，比TPGS高30倍。它还表现出高细胞相容性和低于5%的低溶血率，远低于TPGS。这两种含pSar的表面活性剂制剂高效且通用，这些产品很有可能成为新一代临床疏水性药物增溶剂。
