Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China.
Affiliated Hospital of Shandong Academy of Medical Sciences, The Third Affiliated Hospital of Shandong First Medical University, Jinan, China.
Drug Deliv. 2021 Dec;28(1):1962-1971. doi: 10.1080/10717544.2021.1979125.
Betulinic acid (3β-Hydroxy-20(29)-lupaene-28-oic acid, BA) has excellent anti-cancer activity but poor solubility and low bioavailability. To improve the antitumor activity of BA, a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PVCL-PVA-PEG) graft copolymer (Soluplus) encapsulated BA micelle (Soluplus-BA) was fabricated. The Soluplus-BA micelles presented a mean size of 54.77 ± 1.26 nm and a polydispersity index (PDI) of 0.083. The MTT assay results showed that Soluplus-BA micelles increased the inhibitory effect of BA on MDA-MB-231 cells, mainly due to the enhanced accumulation of reactive oxygen species (ROS) and the destruction of mitochondrial membrane potential (MMP). Soluplus-BA micelles induced the DNA double-strand breaks (DSBs) as the γH2AX foci increased. Moreover, Soluplus-BA also inhibited the tube formation and migration of human umbilical vein endothelial cells (HUVECs), and inhibited the neovascularization of the chicken chorioallantoic membrane (CAM). This angiogenesis inhibitory effect may be accomplished by regulating the HIF-1/VEGF-FAK signaling pathway. The study confirmed the improved anti-tumor effect of Soluplus-BA and its inhibitory effect on angiogenesis, demonstrating the possibility of Soluplus-BA as an effective anti-breast cancer drug delivery system.
桦木酸（3β-羟基-20(29)-羽扇豆烷-28-酸，BA）具有优异的抗癌活性，但溶解度差，生物利用度低。为了提高 BA 的抗肿瘤活性，制备了聚乙烯吡咯烷酮-醋酸乙烯酯-聚乙二醇（PVCL-PVA-PEG）接枝共聚物（Soluplus）包裹的 BA 胶束（Soluplus-BA）。Soluplus-BA 胶束的平均粒径为 54.77±1.26nm，多分散指数（PDI）为 0.083。MTT 检测结果表明，Soluplus-BA 胶束增加了 BA 对 MDA-MB-231 细胞的抑制作用，这主要归因于活性氧（ROS）的积累增强和线粒体膜电位（MMP）的破坏。Soluplus-BA 胶束诱导 DNA 双链断裂（DSBs），γH2AX 焦点增加。此外，Soluplus-BA 还抑制人脐静脉内皮细胞（HUVEC）的管形成和迁移，并抑制鸡胚绒毛尿囊膜（CAM）的新生血管形成。这种血管生成抑制作用可能是通过调节 HIF-1/VEGF-FAK 信号通路实现的。该研究证实了 Soluplus-BA 提高了抗肿瘤效果及其对血管生成的抑制作用，表明 Soluplus-BA 作为一种有效的抗乳腺癌药物传递系统具有可能性。
