title: Mitomycin C-soybean phosphatidylcholine complex-loaded self-assembled PEG-lipid-PLA hybrid nanoparticles for targeted drug delivery and dual-controlled drug release.
abstract: 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.
authors.affiliation: Research Center of Biomedical Engineering & Department of Biomaterials, College of Materials, Xiamen University , Xiamen 361005, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Hongjie
authors.initials: H
authors.lastname: Wu
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Yang
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Jia
authors.forename: Yanxiu
authors.initials: Y
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Jinyan
authors.initials: J
authors.lastname: Lin
authors.forename: Shichao
authors.initials: S
authors.lastname: Wu
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Hou
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry; D008024:Ligands; D008297:Male; D051379:Mice; D016685:Mitomycin / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry*; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013025:Glycine max / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D008024:Ligands; D010713:Phosphatidylcholines; D011091:Polyesters; D011108:Polymers; D014867:Water; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D016685:Mitomycin