Chitosan hydrochloride/hyaluronic acid nanoparticles coated by mPEG as long-circulating nanocarriers for systemic delivery of mitoxantrone

The purpose of this study was to prepare and investigate long circulating polyelectrolyte nanoparticles (PENPs) based on hydrochloride chitosan (HCS) and hyaluronic acid (HA) coated by methoxy poly(ethylene glycol) (mPEG). Mitoxantrone hydrochloride (MTO) was selected as a model drug. TEM showed that MTO-loaded PENPs (MTO-PENPs) were spherical but MTO-loaded PENPs coated by mPEG (MTO-mPEG-PENPs) had a slightly rough morphology with an average hydrodynamic diameter around 200-240 nm. The EE of MTO-mPEG-PENPs and MTO-PENPs were 99.02% and 98.33%, respectively. DSC thermograms showed MTO existed at the molecular level inside the MTO-mPEG-PENPs. Drug release studies revealed MTO-mPEG-PENPs offered better control over the release of drug than uncoated counterparts. Observations of the pharmacokinetic study reveal that MTO-mPEG-PENPs exhibited significant prolongation in blood circulation of drug compared to MTO-PENPs and MTO solution in rats after intravenous administration. The MRT of MTO increased from 117.83 min (MTO solutions) and 16234 min (MTO-PENPs) to 344.42 min (MTO-mPEG-PENPs). The AUC of MTO in MTO-mPEG-PENPs increased 2.52-fold and 3.41-fold compared to MTO-PENPs and MTO solution, respectively. In conclusion, mPEG coated PENPs based on HCS/HA could present a workable strategy for long-circulating systemic delivery of drugs. (C) 2018 Published by Elsevier B.V.