Formulation of injectable glycyrrhizic acid-hydroxycamptothecin micelles as new generation of DNA topoisomerase I inhibitor for enhanced antitumor activity

Publication date: Available online 13 September 2019Source: International Journal of PharmaceuticsAuthor(s): Jieying Cai, Shiwen Luo, Xueli Lv, Yingguang Deng, Hongyuan Huang, Boxin Zhao, Qing Zhang, Guofeng LiAbstractTo develop a new drug delivery system is one of the useful approaches to break through the limitation of hydroxycamptothecin (HCPT), a typical DNA topoisomerase I (Topo I) inhibitor in clinical appliance. Injectable glycyrrhizic acid-hydroxycamptothecin (GL-HCPT) micelles that were able to dramatically improve the solubility and stability of HCPT were prepared through self-assembly process and evaluated both in vitro and in vivo. With a mean particle size (PS) of 105.7 ± 9.7 nm and a drug loading (DL) of 9.0 ± 1.5%, GL-HCPT micelles were rapidly internalized by HepG2 cells after 1 h, significantly increasing the intracellular accumulation of HCPT. Compared with the current used HCPT injection and HCPT/GL physical mixture, GL-HCPT micelles showed enhanced antitumor activity against liver cancer cells (HepG2 and Huh7) as well as a superior suppression on the tumor growth of HepG2 tumor bearing mice. Interestingly, GL-HCPT micelles gathered in liver and simultaneously reduced the drug accumulation in normal tissues, thereby exhibiting minimal cytotoxicity to human normal liver cells (LO2). Therefore, we offered a convenient and cost-effective strategy to construct an intravenous drug delivery system (GL-HCPT micelles) as new generation of DNA Topo I i...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research