Annoneterogenins(ACGs)在胶质瘤的治疗中具有巨大的潜力,但极不溶并且难以在体内递送。聚(环氧乙烷)-b-聚(环氧丁烷)(PEO-PBO)是一种两亲性聚合物,可以降低单核吞噬细胞系统对纳米颗粒的清除。探索一种高效、安全的脑胶质瘤纳米药物,以PEO-PBO为载体构建了负载ACGs的纳米胶束(ACGs/EB-NCs),并比较了PEO-PBO含量对靶向和抗胶质瘤活性的影响。ACG/EB5-NC,ACGs/EB10-NCs和ACGs/EB20-NCs,用不同的ACG/EB进料比制备的三种纳米颗粒,平均粒径为148.8±0.5nm,32.7±4.1nm,和27.1±0.3nm,分别。三个ACG/EB-NC呈球形,载药量接近理论载药量,封装效率大于97%,在生理介质中具有良好的稳定性。ACGs/EB5-NC的累积释放率,ACGs/EB10-NC和ACGs/EB20-NC为78.2%,63.4%,在216小时内占56.3%,分别。三种ACGs/EB-NCs对U87MG细胞的抑制作用相似且强于游离ACGs(P<0.05)。半抑制浓度为0.17、0.18和0.16ng/mL(P>0.05),分别。在U87MG荷瘤小鼠中,ACG/EB5-NC,ACGs/EB10-NC与ACGs/EB20-NC表现出相似的抑瘤率61.1±5.9%,56.2±8.6%和64.3±9.4%(P>0.05),具有良好的安全性。三种ACGs/EB-NC表现出优异的肝脏逃逸能力和肿瘤靶向能力,肿瘤靶向指数大于1.5。成功制备了三种具有强抗胶质瘤活性和肿瘤靶向性的ACGs/EB-NCs,有望为胶质瘤的临床治疗提供新的选择。胶束中PEO-PBO的含量对ACGs/EB-NCs的肿瘤靶向性和抗胶质瘤活性没有显著影响。
Annonaceous acetogenins (ACGs) have great potential in the treatment of gliomas, but are extremely insoluble and difficult for delivery in vivo. Poly(ethylene oxide)-b-poly(butylene oxide) (PEO-PBO) is an amphiphilic polymer and can reduce the clearance of nanoparticles by mononuclear phagocyte system. To explore an efficient and safe nanomedicine for glioma, ACGs-loaded
nanomicelles (ACGs/EB-NCs) was constructed using PEO-PBO as a carrier, and the effect of PEO-PBO content on the targeting and anti-glioma activity were also compared. ACGs/EB5-NCs, ACGs/EB10-NCs and ACGs/EB20-NCs, the three nanomicellels prepared with different ACGs/EB feeding ratios, had average particle sizes of 148.8±0.5 nm, 32.7±4.1 nm, and 27.1±0.3 nm, respectively. The three ACGs/EB-NCs were spherical in shape, with drug loading content close to the theoretical drug loading content, encapsulation efficiency greater than 97 %, and good stability in physiological media. The cumulative release rates of ACGs/EB5-NCs, ACGs/EB10-NCs and ACGs/EB20-NCs were 78.2 %, 63.4 %, and 56.3 % within 216 hours, respectively. The inhibitory effects of three ACGs/EB-NCs on U87 MG cells were similar and stronger than free ACGs (P<0.05), with half inhibitory concentration of 0.17, 0.18, and 0.16 ng/mL (P>0.05), respectively. In U87 MG tumor‑bearing mice, ACGs/EB5-NC, ACGs/EB10-NCs and ACGs/EB20-NCs showed a similar tumor inhibition rate of 61.1±5.9 %, 56.2±8.6 % and 64.3±9.4 % (P>0.05), with good safety. Three ACGs/EB-NCs exhibited excellent liver escape ability and tumor targeting ability, with the tumor targeting index greater than 1.5. Three ACGs/EB-NCs were successfully prepared with strong anti-glioma activity and tumor targeting properties, which are expected to provide new options for the clinical treatment of gliomas. The content of PEO-PBO in micelles did not have a significant effect on the tumor targeting and anti-glioma activity of ACGs/EB-NCs.