The 70th Anniversary of Glucocorticoids in Rheumatic Diseases

The Second Youth of an Old Friend

Yannick Palmowski; Thomas Buttgereit; Frank Buttgereit

Disclosures

Rheumatology. 2019;58(4):580-587. 

In This Article

Liposomal GC

Another approach relying on encapsulation of the conventional drug, although targeting a completely different goal, is liposomal GCs. Liposomes are small vesicles belonging to the group of organic nanoparticles that are composed of a phospholipid bilayer in which conventional GCs can be enclosed. They can be used as drug delivery systems to improve pharmacokinetics and pharmacodynamics while at the same time offering the advantage of being biocompatible and biodegradable.[49] The primary benefit of liposomal GCs lies in their accumulation at sites of inflammation. This permits very high concentrations directly at the inflamed joints or other affected sites while reducing the required systemic dose and thereby minimizing undesired effects on other organs and tissues. Several animal studies have shown very promising results supporting this hypothesis. For example, studies in murine models of RA (collagen type II–induced as well as adjuvant-induced arthritis) demonstrated a lasting resolution of joint inflammation for a single injection of 10 mg/kg liposomal GC, whereas even repeated daily injections with the same dose of free prednisone showed only slight effectiveness.[50,51] Another study compared the therapeutic efficacy of two different liposomal GCs (methylprednisolone hemisuccinate and betamethasone hemisuccinate) in rats with adjuvant-induced arthritis to that of the free agents and two TNF-α inhibitors (infliximab and etanercept). Both liposomal GCs suppressed arthritis significantly better than even higher doses of the free drugs or the TNF-α inhibitors.[52] In a further study, the same research group has recently demonstrated a significant superiority of liposomal GCs compared with the free agent for several outcomes, including survival, in a mouse model of SLE.[53] However, notwithstanding the high hopes raised by all these promising results, what is still entirely lacking to date is evidence on the effects on human patients. The search for respective studies (www.clinicaltrials.gov) merely yields two so far unpublished studies, one of which has already been marked as completed since 2008 (NCT00241982) and one which is currently still recruiting (NCT02534896).

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