School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Liposome Res. 2012 Jun;22(2):110-9. doi: 10.3109/08982104.2011.627514. Epub 2012 Feb 28.
Curcumin (CUR), a plant-derived compound, exhibits versatile antitumor effects. However, its poor hydrophilic property limits its application. To circumvent these drawbacks, we encapsulated CUR in liposomes modified with folic acid for better solubility and enhanced tumor targeting. This novel formulation was prepared by a film-dispersion method and characterized by size, zeta potential, drug-loading efficiency, and physical-condition stability. In vitro, cellular uptake efficiency, cytotoxicity, and apoptosis analysis by flow cytometry were performed to evaluate tumor targeting and killing ability. Results showed that the folate-receptor (FR)-targeted liposomal CUR (F-CUR-L) performed with improved solubility, sufficient stability, and enhanced antitumor activity. Mean diameter, zeta potential, and drug-loading efficiency were 182 nm, -26 mV, and 68%, respectively, and this formulation exhibited stability in storage at 4 °C for 1 month. In vitro, FR-positive cells endocytosed more F-CUR-L than nontargeted liposomal CUR (CUR-L); thus, the former induced more cellular proliferation inhibition and higher apoptosis than the latter, and the enhanced targeting could be hindered by 1 mM of free folic acid. Further, KB cells were more sensitive to F-CUR-L, compared to Hela cells. Finally, the two kinds of tumor cells treated with F-CUR-L also showed dose- and time-dependent apoptosis.
姜黄素（CUR）是一种植物衍生的化合物，具有多种抗肿瘤作用。然而，其较差的亲水性限制了其应用。为了克服这些缺点，我们将 CUR 包封在经过叶酸修饰的脂质体中，以提高其溶解度和增强肿瘤靶向性。该新型制剂采用薄膜分散法制备，并对其粒径、Zeta 电位、载药量和物理稳定性进行了表征。体外细胞摄取效率、细胞毒性和流式细胞术分析细胞凋亡来评估肿瘤靶向和杀伤能力。结果表明，叶酸受体（FR）靶向脂质体姜黄素（F-CUR-L）具有提高的溶解度、足够的稳定性和增强的抗肿瘤活性。平均粒径、Zeta 电位和载药量分别为 182nm、-26mV 和 68%，该制剂在 4°C 下储存 1 个月稳定。体外实验中，FR 阳性细胞内吞的 F-CUR-L 多于非靶向脂质体 CUR（CUR-L）；因此，前者诱导的细胞增殖抑制和凋亡率高于后者，而增强的靶向性可被 1mM 游离叶酸所阻碍。此外，KB 细胞对 F-CUR-L 的敏感性高于 Hela 细胞。最后，两种肿瘤细胞经 F-CUR-L 处理后也表现出剂量和时间依赖性凋亡。
