Glutathione-PEGylated liposomal methylprednisolone in comparison to free methylprednisolone: slow release characteristics and prolonged lymphocyte depression in a first-in-human study

Br J Clin Pharmacol. 2018 May;84(5):1020-1028. doi: 10.1111/bcp.13525. Epub 2018 Mar 9.


Aims: Intravenous high-dose free methylprednisolone (MP) hemisuccinate is the primary treatment for an acute relapse in relapsing-remitting multiple sclerosis. However, it is inconvenient and its side effects are undesirable. Both dose and dosing frequency can be reduced by incorporating free MP in glutathione-PEGylated liposomes, creating a slow-release formulation with reduced toxicity and prolonged peripheral efficacy. This first-in-human study was designed to assess the safety, pharmacokinetics and pharmacodynamics of glutathione-PEGylated liposomes containing MP (2B3-201).

Methods: The first part was a double-blind, three-way cross over study in 18 healthy male subjects, receiving ascending doses of 2B3-201, active comparator (free MP) or placebo. Part 2 of the study was an open-label infusion of 2B3-201 (different doses), exploring pretreatment with antihistamines and different infusion schedules in another 18 healthy male subjects, and a cross-over study in six healthy female subjects. MP plasma concentrations, lymphocyte counts, adrenocorticotropic hormone, osteocalcin and fasting glucose were determined. Safety and tolerability profiles were assessed based on adverse events, safety measurements and central nervous system tests.

Results: The most frequent recorded AE related to 2B3-201 was an infusion related reaction (89%). 2B3-201 was shown to have a plasma half-life between 24 and 37 h and caused a prolonged decrease in the lymphocyte count, adrenocorticotropic hormone and osteocalcin, and a rise in fasting glucose.

Conclusion: 2B3-201 is considered safe, with no clinically relevant changes in central nervous system safety parameters and no serious adverse events. In addition, 2B3-201 shows a long plasma half-life and prolonged immunosuppressive effects.

Keywords: liposomes; methylprednisolone; multiple sclerosis.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Adult
  • Anti-Allergic Agents / therapeutic use
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacokinetics
  • Blood Glucose
  • Clemastine / therapeutic use
  • Cross-Over Studies
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Compounding / methods
  • Drug Therapy, Combination / adverse effects
  • Female
  • Glutathione / chemistry*
  • Healthy Volunteers
  • Humans
  • Liposomes / adverse effects
  • Liposomes / chemistry*
  • Liposomes / pharmacokinetics
  • Liposomes / pharmacology
  • Lymphocyte Count
  • Male
  • Methylprednisolone / adverse effects
  • Methylprednisolone / chemistry
  • Methylprednisolone / pharmacokinetics*
  • Methylprednisolone / pharmacology*
  • Osteocalcin / blood
  • Polyethylene Glycols / chemistry


  • Anti-Allergic Agents
  • Anti-Inflammatory Agents
  • Blood Glucose
  • Delayed-Action Preparations
  • Liposomes
  • Osteocalcin
  • Polyethylene Glycols
  • Adrenocorticotropic Hormone
  • Clemastine
  • Glutathione
  • Methylprednisolone