International Journal of Nanomedicine (Jul 2016)
Annonaceous acetogenins nanosuspensions stabilized by PCL–PEG block polymer: significantly improved antitumor efficacy
Abstract
Jingyi Hong,1,* Yanhong Li,1,2,* Yijing Li,1 Yao Xiao,1,2 Haixue Kuang,2 Xiangtao Wang1 1Key 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, 2School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China *These authors contributed equally to this work Abstract: Annonaceous acetogenins (ACGs) have shown superior antitumor activity against a variety of cancer cell lines, but their clinical application has been limited by their poor solubility. In this study, ACGs-nanosuspensions (NSps) were successfully prepared by a precipitation ultrasonic method using monomethoxypoly (ethylene glycol)2000–poly (ε-caprolactone)2000 (mPEG2000–PCL2000) as a stabilizer. The resultant ACGs-NSps had a mean particle size of 123.2 nm, a zeta potential of -20.17 mV, and a high drug payload of 73.68%. ACGs-NSps were quite stable in various physiological solutions, and they exhibited sustained drug release. Compared to free drug, ACGs-NSps exhibited stronger cytotoxicity against 4T1, MCF-7, and HeLa cells. An in vivo real-time biodistribution investigation after labeling with 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide, a noninvasive near-infrared fluorescence probe, demonstrated that ACGs-NSps could effectively accumulate in tumor. An in vivo antitumor activity study in 4T1 tumor-bearing mice revealed that ACGs-NSps achieved much better therapeutic efficacy than the traditional dosage form (oil solution) even at 1/10 of the dose (74.83% vs 45.53%, P<0.05), demonstrating that NSp was a good dosage form for ACGs to treat cancer. Keywords: annonaceous acetogenins, mPEG2000–PCL2000, near–infrared fluorescence, biodistribution, antitumor efficacy
