Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX 78363, USA.
Colloids Surf B Biointerfaces. 2013 Dec 1;112:350-5. doi: 10.1016/j.colsurfb.2013.07.031. Epub 2013 Aug 2.
Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in human. 17-Allylamino-17-demethoxy geldanamycin (17-AAG) is an inhibitor of heat shock protein 90 (HSP90). The highly lipophilic nature and selective targeting of tumor cells makes 17-AAG a promising candidate for therapy of GBMs but poor water solubility, short biological half-life and hepatotoxicity limited its clinical use. Polymeric mixed micelles composed of Pluronic® P-123 and F-127 (2:1 (w/w)) containing 17-AAG were prepared and characterized. Cellular uptake and in vitro cytotoxicity of the prepared micelles were determined in U87MG human glioblastoma cells. The particle size of 17-AAG loaded Pluronic(®) P-123 and F-127 mixed micelles was 22.2 ± 0.1 nm; drug loading was about 4.0 ± 0.5% (w/w) with 88.2 ± 3.1% (w/w) encapsulation efficiency. About 90% of drug was released from the nanoparticles over 8 days. Cellular uptake studies showed intracellular uptake of mixed micelles. Cytotoxicity study showed 5-fold increase (P < 0.05, n = 3) in the cytotoxicity of 17-AAG-loaded mixed micelles to free 17-AAG. Due to their targeting ability, size, high drug loading and controlled release behavior, 17-AAG loaded Pluronic(®) P-123 and F-127 mixed micelles might be developed as a delivery system for GBM treatment.
多形性胶质母细胞瘤（GBM）是人类最常见和侵袭性最强的原发性脑肿瘤。17- 烯丙基-17- 去甲氧基格尔德霉素（17-AAG）是热休克蛋白 90（HSP90）的抑制剂。17-AAG 具有高度亲脂性和对肿瘤细胞的选择性靶向作用，使其成为治疗 GBM 的有前途的候选药物，但较差的水溶性、较短的生物半衰期和肝毒性限制了其临床应用。由 Pluronic® P-123 和 F-127（2:1（w/w））组成的聚合物混合胶束含有 17-AAG 被制备和表征。在 U87MG 人胶质母细胞瘤细胞中测定了制备的胶束的细胞摄取和体外细胞毒性。载有 17-AAG 的 Pluronic® P-123 和 F-127 混合胶束的粒径为 22.2 ± 0.1nm；载药量约为 4.0 ± 0.5%（w/w），包封效率为 88.2 ± 3.1%（w/w）。约 90%的药物在 8 天内从纳米颗粒中释放出来。细胞摄取研究表明混合胶束的细胞内摄取。细胞毒性研究表明，载有 17-AAG 的混合胶束对游离 17-AAG 的细胞毒性增加了 5 倍（P < 0.05，n = 3）。由于其靶向能力、大小、高载药量和控制释放行为，载有 17-AAG 的 Pluronic® P-123 和 F-127 混合胶束可开发为治疗 GBM 的递送系统。
