Amphiphilic drugs as surfactants to fabricate excipient-free stable nanodispersions of hydrophobic drugs for cancer chemotherapy.
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 25 mg/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.
Center for Bio-nanoengineering, Key Laboratory of Biomass Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
Shiqi
S
Hu
Utah-Inha DDA & Advanced Therapeutics Research Center, Incheon 406840, South Korea.
Eunhye
E
Lee
College of Materials Science and Opto-Electronic Technology, University of Chinese Academy of Sciences, Beijing 100049, China.
Chi
C
Wang
Center for Bio-nanoengineering, Key Laboratory of Biomass Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
Jinqiang
J
Wang
Center for Bio-nanoengineering, Key Laboratory of Biomass Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
Zhuxian
Z
Zhou
Utah-Inha DDA & Advanced Therapeutics Research Center, Incheon 406840, South Korea.
Yixian
Y
Li
College of Materials Science and Opto-Electronic Technology, University of Chinese Academy of Sciences, Beijing 100049, China.
Xiaoyi
X
Li
Center for Bio-nanoengineering, Key Laboratory of Biomass Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
Jianbin
J
Tang
Utah-Inha DDA & Advanced Therapeutics Research Center, Incheon 406840, South Korea.
Don Haeng
DH
Lee
Center for Bio-nanoengineering, Key Laboratory of Biomass Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
Xiangrui
X
Liu
Center for Bio-nanoengineering, Key Laboratory of Biomass Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address: shenyq@zju.edu.cn.
Youqing
Y
Shen
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D005079:Excipients; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D000077146:Irinotecan; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*
D000970:Antineoplastic Agents; D005079:Excipients; D013501:Surface-Active Agents; D000077146:Irinotecan; D002166:Camptothecin
7-Ethyl-10-hydroxycamptothecin (SN38); Excipient-free; Nanodispersion; Nanomedicine; Water-insoluble drugs