Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.
Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Carbohydr Polym. 2017 Sep 15;172:130-141. doi: 10.1016/j.carbpol.2017.05.007. Epub 2017 May 6.
In the present work, new self-assembled nanoparticles (NPs) were engineered using biocompatible and biodegradable natural polymer, chitosan (CS). The complexation of CS with sodium dodecyl sulfate (SDS) facilitated the regioselective chemical modification of CS hydroxyl groups with maleic anhydride, and produced polymerizable precursor of CS that was further grafted with N-isopropylacrylamide (NIPAAm) as temperature-sensitive moiety and oleic acid (OA) as hydrophobic monomer. After removal of SDS complex, the free amino groups were functionalized with folic acid (FA) to form folate-(PNIPAAm-co-OA)-g-CS micellar NPs. The NPs were loaded with a tyrosine kinase inhibitor erlotinib (ETB), which was carried out above the lower critical solution temperature (LCST) of micelles solution. The structure, size distribution, zeta potential, thermal stability, elemental composition, morphology and LCST of the synthesized micelles were characterized. The cellular uptake and cell cytotoxicity analyses revealed that the developed smart folate-(PNIPAAm-co-OA)-g-CS micellar NPs could be used for effective cancer therapy as an injectable tumor targeting nanocarrier.
在本工作中，使用生物相容性和可生物降解的天然聚合物壳聚糖 (CS) 设计了新的自组装纳米颗粒 (NPs)。CS 与十二烷基硫酸钠 (SDS) 的络合促进了 CS 羟基的区域选择性化学修饰与马来酸酐的反应，生成了可聚合的 CS 前体，进一步接枝 N-异丙基丙烯酰胺 (NIPAAm) 作为温度敏感部分和油酸 (OA) 作为疏水性单体。除去 SDS 络合物后，游离氨基用叶酸 (FA) 官能化，形成叶酸-(PNIPAAm-co-OA)-g-CS 胶束 NPs。在胶束溶液的低临界溶解温度 (LCST) 以上进行载酪氨酸激酶抑制剂厄洛替尼 (ETB)。对合成胶束的结构、粒径分布、Zeta 电位、热稳定性、元素组成、形态和 LCST 进行了表征。细胞摄取和细胞毒性分析表明，开发的智能叶酸-(PNIPAAm-co-OA)-g-CS 胶束 NPs 可用作有效的癌症治疗的可注射肿瘤靶向纳米载体。
