Targeted Cancer Therapy With Novel High Drug-Loading Nanocrystals
Targeted Cancer Therapy With Novel High Drug-Loading Nanocrystals
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DOI：
10.1002/jps.22112
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发表时间：
2010-08-01
影响因子：
3.8
通讯作者：
Huang, Leaf
中科院分区：
文献类型：
--
作者：
Liu, Feng;Park, Ji-Young;Huang, Leaf
开发了一种用于治疗癌症的新型疏水性药物的微球制剂。该新方法称为三相纳米颗粒工程技术（3 PNET），包括三个阶段：第一阶段，无定形沉淀，第二阶段，水合无定形聚集体，第三阶段，水化无定形聚合体，第四阶段，水化无定形聚合体。和3期，稳定的紫杉醇3 PNET已应用于两种抗癌药物，紫杉醇（PTX）和喜树碱（CPT），使用Pluronic F127（F127）聚合物作为单一赋形剂。纳米晶体以高的药物与赋形剂的比率包封超过99%的药物。PTX的微胶囊制剂在微胶囊相关浓度下不诱导溶血。在人肺癌和小鼠乳腺癌两种肿瘤模型中的抗肿瘤活性表明，静脉注射纳米晶体显着抑制肿瘤生长。纳米晶体还显示出通过口服给药的显著治疗效果。此外，纳米晶体可以通过将叶酸配体缀合至F127来进一步修饰用于靶向递送PTX。新的纳米药物制剂显示出明显的临床开发潜力，因为其具有优异的抗肿瘤活性、低毒性和易于放大生产。该制剂方法可应用于其他疏水性药物（C）2010 Wiley-Liss，Inc and the American Pharmacological Association J Pharm Sci 99 3542- 3551，2010
A novel nanocrystal formulation of hydrophobic drugs has been developed for cancer therapy The new method, called a three-phase nanoparticle engineering technology (3PNET), includes three phases: phase 1, amorphous precipitate; phase 2, hydrated amorphous aggregate; and phase 3, stabilized nanocrystal The 3PNET has been applied to two anticancer drugs, paclitaxel (PTX) and camptothecin (CPT), using Pluronic F127 (F127) polymer as a single excipient. The nanocrystals encapsulated over 99% of the drug with a high ratio of drug to excipient The nanocrystal formulation of PTX did not induce hemolysis at pharmacologically relevant concentrations. Antitumor activity in two tumor models, human lung cancer and murine breast cancer, demonstrated that intravenously injected nanocrystals significantly inhibited the tumor growth. The nanocrystals also showed significant therapeutic effects via oral administration In addition, the nanocrystals could be further modified for targeted delivery of PTX by conjugating a folate ligand to F127. The new nanomedicine formulations show clear potential for clinical development because of the excellent antitumor activity, low toxicity, and the ease of scale-up manufacture The formulation method may apply to other hydrophobic drugs (C) 2010 Wiley-Liss, Inc and the American Pharmacists Association J Pharm Sci 99 3542-3551,2010