Polysaccharide-based nanoparticles for co-loading mitoxantrone and verapamil to overcome multidrug resistance in breast tumor

Abstract

Yurui Xu,1 Sajid Asghar,2 Shiya Gao,1 Zhipeng Chen,3 Lin Huang,1 Lining Yin,1 Qineng Ping,1 Yanyu Xiao11Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan; 3Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China Abstract: The aim of this study was to evaluate the potential of polyelectrolyte complex nanoparticles (PENPs) based on hyaluronic acid/chitosan hydrochloride (HA/HCS) for co-loading mitoxantrone (MTO) and verapamil (VRP) to overcome multidrug resistance in breast tumors. PENPs co-loaded with MTO and VRP (MTO-VRP-PENPs) were affected by the method of preparation, molecular weight of HA, mass ratios and initial concentrations of HA/HCS, pH, and drug quantities. Optimized MTO-VRP-PENPs were ~209 nm in size with a zeta potential of approximately −24 mV. Encapsulation efficiencies (%) of MTO and VRP were 98.33%±0.27% and 44.21%±8.62%, respectively. MTO and VRP were successfully encapsulated in PENPs in a molecular or amorphous state. MTO-VRP-PENPs showed significant cytotoxicity in MCF-7/ADR cells in contrast to MTO-loaded PENPs (MTO-PENPs). The reversal index of MTO-VRP-PENPs was 13.25 and 10.33 times greater than that of the free MTO and MTO-PENPs, respectively. In conclusion, MTO-VRP-PENPs may serve as a promising carrier to overcome tumor drug resistance.Keywords: hyaluronic acid, chitosan hydrochloride, mitoxantrone hydrochloride, verapamil hydrochloride, co-delivery, multidrug resistance

Keywords

• Hyaluronic acid
• Chitosan hydrochloride
• Mitoxantrone hydrochloride
• Verapamil hydrochloride
• Co-delivery
• Multi-drug resistance.