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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.
AuthorsYang Li, Hongjie Wu, Xiangrui Yang, Mengmeng Jia, Yanxiu Li, Yu Huang, Jinyan Lin, Shichao Wu, Zhenqing Hou
JournalMolecular pharmaceutics (Mol Pharm) Vol. 11 Issue 8 Pg. 2915-27 (Aug 04 2014) ISSN: 1543-8392 [Electronic] United States
PMID24984984 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Ligands
  • Phosphatidylcholines
  • Polyesters
  • Polymers
  • Water
  • Lactic Acid
  • Polyethylene Glycols
  • poly(lactide)
  • Mitomycin
Topics
  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • Drug Delivery Systems
  • HeLa Cells
  • Hemolysis (drug effects)
  • Humans
  • Hydrogen-Ion Concentration
  • Lactic Acid (chemistry)
  • Ligands
  • Male
  • Mice
  • Mitomycin (chemistry)
  • Nanoparticles (chemistry)
  • Neoplasm Transplantation
  • Particle Size
  • Phosphatidylcholines (chemistry)
  • Polyesters
  • Polyethylene Glycols (chemistry)
  • Polymers (chemistry)
  • Rats
  • Rats, Sprague-Dawley
  • Solubility
  • Soybeans (chemistry)
  • Water (chemistry)

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