Most present
drug-
phospholipid delivery systems were based on a water-insoluble
drug-
phospholipid complex but rarely water-soluble
drug-
phospholipid complex.
Mitomycin C (MMC) is a water-soluble anticancer
drug extensively used in first-line
chemotherapy but is limited by its poor aqueous stability in vitro, rapid elimination from the body, and lack of target specificity. In this article, we report the MMC-soybean
phosphatidylcholine complex-loaded PEG-
lipid-PLA hybrid nanoparticles (NPs) with
Folate (FA) functionalization (FA-
PEG-PE-PLA NPs@MMC-SPC) for targeted
drug delivery and dual-controlled drug release. FA-
PEG-PE-PLA NPs@MMC-SPC comprise a hydrophobic core (PLA) loaded with MMC-SPC, an amphiphilic
lipid interface layer (PE), a hydrophilic shell (PEG), and a targeting
ligand (FA) on the surface, with a spherical shape, a nanoscaled particle size, and high
drug encapsulation efficiency of almost 95%. The advantage of the new drug delivery systems is the early phase controlled drug release by the
drug-
phospholipid complex and the late-phase controlled drug release by the pH-sensitive
polymer-
lipid hybrid NPs. In vitro cytotoxicity and
hemolysis assays demonstrated that the
drug carriers were cytocompatible and hemocompatible. The pharmacokinetics study in rats showed that FA-
PEG-PE-PLA NPs@MMC-SPC significantly prolonged the blood circulation time compared to that of the free MMC. More importantly, FA-
PEG-PE-PLA NPs@MMC-SPC presented the enhanced cell uptake/cytotoxicity in vitro and superior
tumor accumulation/therapeutic efficacy in vivo while reducing the systemic toxicity. A significant accumulation of MMC in the nuclei as the site of MMC action achieved in FA-
PEG-PE-PLA NPs@MMC-SPC made them ideal for MMC
drug delivery. This study may provide an effective strategy for the design and development of the water-soluble
drug-
phospholipid complex-based targeted
drug delivery and sustained/controlled drug release.