title: Annonaceous acetogenins (ACGs) nanosuspensions based on a self-assembly stabilizer and the significantly improved anti-tumor efficacy.
abstract: Annonaceous acetogenins (ACGs) have exhibited antitumor activity against various cancers. However, these substances' poor solubility has limited clinical applications. In this study, hydroxypropyl-beta-cyclodextrin (HP-β-CD) and soybean lecithin (SPC) were self-assembled into an amphiphilic complex. ACGs nanosuspensions (ACGs-NSps) were prepared with a mean particle size of 144.4nm, a zeta potential of -22.9mV and a high drug payload of 46.17% using this complex as stabilizer. The ACGs-NSps demonstrated sustained release in vitro and good stability in plasma as well as simulated gastrointestinal fluid, and met the demand of both intravenous injection and oral administration. The ACGs-NSps demonstrated significantly increased cytotoxicity against Hela and HepG2 cancer cell lines compared to ACGs in solution (in vitro cytotoxicity assay). An in vivo study with H22-tumor bearing mice demonstrated that nanosuspensions significantly improved ACGs' antitumor activity. When orally administered, ACGs-NSps achieved a similar tumor inhibition rate at 1/10th the dose of ACGs in an oil solution (47.94% vs. 49.74%, p>0.05). Improved therapeutic efficacy was further achieved when the ACGs-NSps were intravenously injected into mice (70.31%). With the help of nanosuspension technology, ACGs may be an effective antitumor drug for clinic use.
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. Electronic address: hongjingyi513@163.com.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Hong
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; Heilongjiang University of Chinese Medicine, School of Pharmacy, Harbin 15004, China. Electronic address: liyanhong936346812@163.com.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; Heilongjiang University of Chinese Medicine, School of Pharmacy, Harbin 15004, China. Electronic address: 18811545437@163.com.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. Electronic address: yjli920730@163.com.
authors.forename: Yijing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. Electronic address: ffguo@163.com.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Heilongjiang University of Chinese Medicine, School of Pharmacy, Harbin 15004, China. Electronic address: hxkuang56@163.com.
authors.forename: Haixue
authors.initials: H
authors.lastname: Kuang
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. Electronic address: xtaowang@163.com.
authors.forename: Xiangtao
authors.initials: X
authors.lastname: Wang
mesh_terms: D054378:Acetogenins / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D065546:Drug Liberation; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D013535:Suspensions / Q000737:chemistry*
chemical_list: D054378:Acetogenins; D000970:Antineoplastic Agents; D013535:Suspensions
keywords: Annonaceous acetogenins; Anti-tumor activity; Cyclodextrin; Nanosuspensions; Self-assembly stabilizer