Erythrocyte Membrane-Enveloped Salvianolic Acid B Nanoparticles Attenuate Cerebral Ischemia-Reperfusion Injury

Int J Nanomedicine. 2022 Aug 10:17:3561-3577. doi: 10.2147/IJN.S375908. eCollection 2022.

Abstract

Purpose: Ischemic stroke is the second leading cause of death and the third leading cause of disability worldwide. Salvianolic acid B (SAB), a water-soluble phenolic acid derived from the traditional Chinese medicine Salvia miltiorrhiza, exerted protective effects on cerebral ischemia-reperfusion injury. However, the efficacy of SAB is seriously hindered by poor blood brain barrier (BBB) permeability and short biological half-life in plasma. Brain targeted biomimetic nanoparticle delivery systems offer much promise in overcoming these limitations.

Methods: A brain targeted biomimetic nanomedicine (RR@SABNPs) was developed, which comprised of SAB loaded bovine serum albumin nanoparticles and functionalized red blood cell membrane (RBCM) with Arg-Gly-Asp (RGD). The characterization parameters, including particle size, zeta potential, morphology, Encapsulation Efficiency (EE), Drug Loading (DL), release behavior, stability, and biocompatibility, were investigated. Moreover, the middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was used to assess the therapeutic efficacy of RR@SABNPs on ischemic stroke. Finally, the reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were detected by DHE and JC‑1 staining in oxygen-glucose deprivation/reperfusion (OGD/R) and H2O2 injured PC12 cells.

Results: RR@SABNPs exhibited spheric morphology with core-shell structures and good stability and biocompatibility. Meanwhile, RR@SABNPs can significantly prolong SAB circulation time by overcoming the reticuloendothelial system (RES) and actively targeting ischemic BBB. Moreover, RR@SABNPs had comprehensive protective effects on MCAO/R model mice, manifested as a reduced infarct volume and improved neurological and sensorimotor functions, and significantly scavenged excess ROS and maintained MMP.

Conclusion: The designed brain targeted biomimetic nanomedicine RR@SABNPs can significantly prolong the half-time of SAB, deliver SAB into the ischemic brain and exhibit good therapeutic effects on MCAO/R model mice.

Keywords: blood brain barrier; long circulation; mitochondrial membrane potential; reactive oxygen species; red blood cell membrane.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Benzofurans
  • Brain Ischemia* / drug therapy
  • Erythrocyte Membrane / metabolism
  • Hydrogen Peroxide
  • Infarction, Middle Cerebral Artery / drug therapy
  • Ischemic Stroke*
  • Mice
  • Nanoparticles* / chemistry
  • Rats
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / metabolism

Substances

  • Benzofurans
  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • salvianolic acid B