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Amphiphilic drugs as surfactants to fabricate excipient-free stable nanodispersions of hydrophobic drugs for cancer chemotherapy

Hu, Shiqi, Lee, Eunhye, Wang, Chi, Wang, Jinqiang, Zhou, Zhuxian, Li, Yixian, Li, Xiaoyi, Tang, Jianbin, Lee, Don Haeng, Liu, Xiangrui, Shen, Youqing
Journal of Controlled Release 2015 v.220 pp. 175-179
antineoplastic activity, antineoplastic agents, bioavailability, clinical trials, composite polymers, drug therapy, hydrophobicity, nanoparticles, neoplasms, paclitaxel, surfactants, translation (genetics), water solubility
Nanoformulations have been extensively explored to deliver water-insoluble drugs, but they generally use exotic new materials, for instance, amphiphilic block copolymers, which must first go through extensively clinical trials and be approved as drug excipients before any clinical uses. We hypothesize that using clinical amphiphilic drugs as surfactants to self-assemble with and thus solubilize hydrophobic drugs will lead to readily translational nanoformulations as they contain no new excipients. Herein, we show the first example of such excipient-free nanodispersions using an amphiphilic anti-tumor drug, irinotecan hydrochloride (CPT11). CPT11 self-assembles with its insoluble active parent drug, 7-ethyl-10-hydroxy camptothecin (SN38), into stable and water-dispersible nanoparticles, increasing SN38's water solubility by thousands of times up to 25mg/mL with a loading efficiency close to 100%. The versatility of this approach is also demonstrated by fabricating nanodispersions of CPT11 with other water-insoluble drugs including paclitaxel (PTX) and camptothecin (CPT). These nanodispersions have much increased bioavailability and thereby improved anti-cancer activities. Thus, this strategy, using clinically proven amphiphilic drugs as excipients to fabricate nanodispersions, avoids new materials and makes readily translational nanoformulations of hydrophobic drugs.