Protective effects on myocardial infarction model: delivery of schisandrin B using matrix metalloproteinase-sensitive peptide-modified, PEGylated lipid nanoparticles

Int J Nanomedicine. 2017 Sep 26:12:7121-7130. doi: 10.2147/IJN.S141549. eCollection 2017.

Abstract

Purpose: Schisandrin B (Sch B) is clinically applied for the treatment of hepatitis and ischemic disease. However, its clinical efficacy is limited due to the poor solubility and low bioavailability. This study aimed to develop matrix metalloproteinase (MMP)-sensitive peptide-modified, polyethylene glycol (PEG)-modified (PEGylated) solid lipid nanoparticles (SLNs) for loading Sch B (MMP-Sch B SLNs), and to evaluate the therapeutic effect in the myocardial infarction model.

Methods: PEG lipid and MMP-targeting peptide conjugate were synthesized. MMP-Sch B SLNs were prepared by solvent displacement technique. The physicochemical properties and pharmacokinetics of SLNs were investigated. In vivo effects on infarct size was evaluated in rats.

Results: The successful synthesis of lipid-peptide conjugate was confirmed. MMP-Sch B SLNs had a particle size of 130 nm, a zeta potential of 18.3 mV, and a sustained-release behavior. Higher heart drug concentration and longer blood circulation times were achieved by Sch B loaded SLNs than the drug solution according to the pharmacokinetic and biodistribution results. The best therapeutic efficacy was exhibited by MMP-Sch B SLNs by reducing the infarction size to the greatest extent.

Conclusion: The modified SLNs may be a good choice for delivery of Sch B for the treatment of myocardial infarction.

Keywords: CVDs; cardiovascular diseases; lipid nanoparticles; matrix metalloproteinase; schisandrin B.

MeSH terms

  • Animals
  • Biological Availability
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Cell Death / drug effects
  • Cyclooctanes / blood
  • Cyclooctanes / pharmacokinetics
  • Cyclooctanes / pharmacology
  • Cyclooctanes / therapeutic use
  • Disease Models, Animal
  • Drug Delivery Systems
  • Drug Liberation
  • Humans
  • Lignans / blood
  • Lignans / pharmacokinetics
  • Lignans / pharmacology
  • Lignans / therapeutic use*
  • Lipids / chemistry*
  • Matrix Metalloproteinases / metabolism*
  • Myocardial Infarction / blood
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology
  • Nanoparticles / chemistry*
  • Particle Size
  • Peptides / chemistry*
  • Polycyclic Compounds / blood
  • Polycyclic Compounds / pharmacokinetics
  • Polycyclic Compounds / pharmacology
  • Polycyclic Compounds / therapeutic use*
  • Polyethylene Glycols / chemistry*
  • Proton Magnetic Resonance Spectroscopy
  • Rats, Sprague-Dawley
  • Tissue Distribution / drug effects

Substances

  • Cardiotonic Agents
  • Cyclooctanes
  • Lignans
  • Lipids
  • Peptides
  • Polycyclic Compounds
  • schizandrin B
  • Polyethylene Glycols
  • Matrix Metalloproteinases