posted on 2019-12-03, 17:42authored byYawei Du, Zhi Wang, Tao Wang, Wei He, Wenya Zhou, Man Li, Chen Yao, Xinsong Li
The microtubule inhibitor paclitaxel (PTX) is used to
treat a wide
range of solid tumors. Due to the poor aqueous solubility of PTX,
a continuous demand for safe, efficient PTX formulations with improved
antitumor activity exists. Here, we report a novel form of redox-sensitive
paclitaxel (PTX)-encapsulated liposomes based on the previously developed
disulfide phosphatidylcholine (SS-PC). PTX-loaded stealth liposomes
(PTX/SS-LP) composed of SS-PC, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG2000 (DSPE-PEG2000), and cholesterol were prepared
using the reverse-phase evaporation method. The characterization of
the PTX/SS-LP liposomes using dynamic light scattering and transmission
electron microscopy confirmed their uniform particle size and typical
unilamellar vesicle structure with an average bilayer thickness of
approximately 4 nm. Changes in the size and morphology as well as
the rapid release of PTX triggered by the addition of dithiothreitol
revealed the redox sensitivity of PTX/SS-LP. Finally, evaluations
in MCF-7 and A549 cells in vitro and in BALB/c mice in vivo revealed the improved anticancer efficiency, biodistribution,
and safety of PTX/SS-LP compared with those of Taxol and nonredox-sensitive
PTX/LP. In conclusion, PTX/SS-LP displays a redox-responsive release
of paclitaxel with improved antitumor activity and has great potential
as a next-generation stealth liposomal PTX delivery system.