Enhanced brain delivery of liposomal methylprednisolone improved therapeutic efficacy in a model of neuroinflammation

J Control Release. 2012 Dec 28;164(3):364-9. doi: 10.1016/j.jconrel.2012.06.022. Epub 2012 Jun 23.


Neuroinflammation contributes to a wide range of disorders of the central nervous system (CNS). Of the available anti-inflammatory drugs, only glucocorticoids have shown central efficacy in CNS-related disorders, such as multiple sclerosis (MS). However, their side effects are dose limiting. To optimally improve the therapeutic window of methylprednisolone, we enhanced its CNS delivery by using pegylated liposomes conjugated to the brain-targeting ligand glutathione. In healthy rats, plasma circulation and brain uptake were significantly increased after encapsulating methylprednisolone in glutathione pegylated (GSH-PEG) liposomes. Furthermore, the efficacy of GSH-PEG liposomal methylprednisolone was investigated in rats with acute experimental autoimmune encephalomyelitis (EAE), an animal model of MS; rats received treatment (10mg/kg; i.v. injection), before disease onset, at disease onset, or at the peak of disease. Free methylprednisolone and non-targeted pegylated (PEG) liposomal methylprednisolone served as control treatments. When treatment was initiated at disease onset, free methylprednisolone showed no effect, while GSH-PEG liposomal methylprednisolone significantly reduced the clinical signs to 42±6.4% of saline control. Moreover, treatment using GSH-PEG liposomes was significantly more effective compared to PEG liposomes. Our findings hold promise for MS treatment and warrant further investigations into this brain delivery system for the treatment of neuroinflammation.

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / therapeutic use
  • Brain / drug effects*
  • Brain / metabolism
  • Drug Carriers / chemistry*
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Glutathione / chemistry
  • Liposomes
  • Male
  • Methylprednisolone / administration & dosage*
  • Methylprednisolone / pharmacokinetics
  • Methylprednisolone / therapeutic use
  • Polyethylene Glycols / chemistry
  • Rats
  • Rats, Inbred Lew
  • Tissue Distribution


  • Anti-Inflammatory Agents
  • Drug Carriers
  • Liposomes
  • Polyethylene Glycols
  • Glutathione
  • Methylprednisolone