Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles

Abstract

Xue Yuan,1,2 Qian Xie,1 Keyu Su,1 Zhijie Li,3 Dong Dong,3 Baojian Wu1,2 1Research Center for Biopharmaceutics and Pharmacokinetics, College of Pharmacy, 2Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, 3International Ocular Surface Research Centre and Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China Abstract: Arenobufagin (ABG) is a major active component of toad venom, a traditional Chinese medicine used for cancer therapy. However, poor aqueous solubility limits its pharmacological studies in vivo due to administration difficulties. In this study, we aimed to develop a polymeric nanomicelle (PN) system to enhance the solubility of ABG for effective intravenous delivery. ABG-loaded PNs (ABG-PNs) were prepared with methoxy poly (ethylene glycol)-block-poly (D,L-lactic-co-glycolic acid) (mPEG-PLGA) using the solvent-diffusion technique. The obtained ABG-PNs were 105 nm in size with a small polydispersity index of 0.08. The entrapment efficiency and drug loading were 71.9% and 4.58%, respectively. Cellular uptake of ABG-PNs was controlled by specific clathrin-mediated endocytosis. In addition, ABG-PNs showed improved drug pharmacokinetics with an increased area under the curve value (a 1.73-fold increase) and a decreased elimination clearance (37.8% decrease). The nanomicelles showed increased drug concentrations in the liver and lung. In contrast, drug concentrations in both heart and brain were decreased. Moreover, the nanomicelles enhanced the anticancer effect of the pure drug probably via increased cellular uptake of drug molecules. In conclusion, the mPEG-PLGA-based nanomicelle system is a satisfactory carrier for the systemic delivery of ABG. Keywords: bufanolide steroid, arenobufagin, nanomicelles, mPEG-PLGA

Keywords

• Bufanolide steroid
• Arenobufagin
• Nanomicelles
• mPEG-PLGA