Preparation, Characterization, and In Vivo Study of 7-Ethyl-14-Aminocamptothecin-Loaded Poly(Ethylene Glycol)2000 -Poly(Lactic Acid)2000 Polymeric Micelles Against H460 Human Nonsmall Cell Lung Carcinoma

  • J Pharm Sci. 2015 Nov;104(11):3934-3942. doi: 10.1002/jps.24613.
Xia Cheng  1 ,  Neng Qiu  2 ,  Jianhong Yang  1 ,  Huili Liu  3 ,  Jiaolin Wen  1 ,  Wenwen Wang  1 ,  Zhoufeng Wang  1 ,  Lijuan Chen  4
Affiliations
  • 1. State Key laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People's Republic of China.
  • 2. Department of Chemical and Pharmaceutical engineering, College of Materials and Chemistry and Chemical Engineering, Chengdu University of Technology, Chengdu 610059, People's Republic of China.
  • 3. Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, People's Republic of China.
  • 4. State Key laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address: [email protected].
PMID: 26306026 DOI: 10.1002/jps.24613
Abstract

This work aims to improve the solubility of 7-ethyl-14-aminocamptothecin (EACPT) by encapsulating it into monomethoxy poly(ethylene glycol)2000 -poly(lactic acid)2000 (MPEG-PLA) polymeric micelles. Micelles were prepared by a solid dispersion method; the properties including particle size distribution, morphology, drug loading, entrapment efficiency, crystallography property, solubility, and stability were characterized in detail. The results demonstrated that the EACPT-loaded MPEG-PLA polymeric micelle (EACPT-M) was successfully developed with a small particle size of 20.7 ± 0.2 nm, and the solubility was increased approximately 800-fold compared with free drug. In vitro release study showed sustained-release behavior of EACPT-M. Cytotoxicity assay suggested the incorporated EACPT maintained the potent antitumor effect of free drug. Furthermore, the obtained EACPT-M (1 mg/mL) did not induce hemolysis in vitro. Additionally, EACPT-M exhibited significant tumor growth inhibition in H460 human tumor xenograft model. The results indicated that the EACPT-M was a water-soluble, safe, and effective delivery system for human Cancer chemotherapy.

Keywords
7-ethyl-14-aminocamptothecin; PLA; cancer chemotherapy; micelle; solid dispersion; solubility.
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