科研之友
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摘要
Poly (ethylene glycol) (PEG) and its derivatives are not only used to improve the stability of drug-loaded nanoparticles but also prolong their stay in blood for extended durations. We, hereby, report mitoxantrone loaded polyelectrolyte nanoparticles (MTO-PENPs) based on the hyaluronic acid (HA) and chitosan hydrochloride (HCS) complexed with amphiphilic PEG derivatives, carboxylated PEG (100) monostearate (PGMC, MTO-CPENPs) and D-tocopheryl PEG 1000 succinate (TPGS, MTO-TPENPs), to extend the in vivo circulation time. Maximum encapsulation efficiency ( > 95%) was observed at 40 mg/mL of PGMC or TPGS. TEM showed that PENPs preparations were spherical with an average diameter around 200 nm. Both MTO-CPENPs and MTO-TPENPs showed better stability than MTO-PENPs during storage at 4 degrees C, offered better control over the release of drug than simple PENPs, and showed pH-sensitivity with faster drug release in acidic conditions. MTO-CPENPs showed greater aversion from the protein adsorption and phagocytic uptake by macrophages but their cytotoxicity against the cancerous cells was poor of the all, and yet MTO-TPENPs showed good cytotoxicity against the MCF-7 cells. In the pharmacokinetic study, both MTO-CPENPs and MTO-TPENPs exhibited significant prolongation in blood circulation of drug compared to MTO-PENPs and MTO solution in rats after intravenous administration. However, MTO-TPENPs showed no statistically significant difference in plasma profile of MTO than the MTO-CPENPs. This indicates that there are underlying mechanisms that need to be explored to use the PEGylation in a way that could prolong stay of the nanoparticles in blood without compromising their interactions with target cells.
