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Abstract

Background

Glucocorticoids have been known for years to be the most effective therapy in systemic lupus erythematosus. Their use, however, is limited by the need for high doses due to their unfavorable pharmacokinetics and biodistribution. We have previously developed a novel liposome-based steroidal (methylprednisolone hemisuccinate (MPS)) nano-drug and demonstrated its specific accumulation in inflamed tissues, as well as its superior therapeutic efficacy over that of free glucocorticoids (non-liposomal) in the autoimmune diseases, including the adjuvant arthritis rat model and the experimental autoimmune encephalomyelitis mouse model.

Objectives

In the present work we have evaluated the therapeutic effect of the above liposome-based steroidal (MPS) nano-drug in the MRL-lpr/lpr murine model of SLE and compared it with similar doses of the free MPS.

Methods

MRL-lpr/lpr mice were treated with daily injections of free MPS or weekly injections of 10% dextrose, empty nano-liposomes or the steroidal nano-drug and the course of their disease was followed up to the age of 24 weeks.

Results

Treatment with the steroidal nano-drug was found to be significantly superior to the free MPS in suppressing anti-dsDNA antibody levels, proliferation of lymphoid tissue and renal damage, and in prolonging survival of animals.

Conclusion

This significant superiority of our liposome based steroidal nano-drug administered weekly compared with daily injections of free methylprednisolone hemisuccinate in suppressing murine lupus indicates this glucocorticoid nano-drug formulation may be a good candidate for the treatment of human SLE.

Keywords

Systemic lupus erythematosus treatment corticosteroids

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References

Ad Hoc Working Group on Steroid-Sparing Criteria in Lupus. Criteria for steroid-sparing ability of interventions in systemic lupus erythematosus: Report of a consensus meeting. Arthritis Rheum 2004; 50: 3427–3431.

Duru

van der Goes

Jacobs

. EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis 2013; 72: 1905–1913.

Wofsy

. Recent progress in conventional and biologic therapy for systemic lupus erythematosus. Ann Rheum Dis 2013; 72(Suppl. 2): ii66–ii68.

Avnir

Turjeman

Tulchinsky

. Fabrication principles and their contribution to the superior in vivo therapeutic efficacy of nano-liposomes remote loaded with glucocorticoids. PLoS One 2011; 10: e25721–e25721.

Avnir

Ulmansky

Wasserman

. Amphipathic weak acid glucocorticoid prodrugs remote-loaded into sterically stabilized nanoliposomes evaluated in arthritic rats and in a Beagle dog: A novel approach to treating autoimmune arthritis. Arthritis Rheum 2008; 58: 119–129.

Ozbakir

Crielaard

Metselaar

Storm

Lammers

. Liposomal corticosteroids for the treatment of inflammatory disorders and cancer. J Control Release 2014; 190: 624–636.

Quan

Zhang

Crielaard

. Nanomedicines for inflammatory arthritis: Head-to-head comparison of glucocorticoid-containing polymers, micelles, and liposomes. ACS Nano 2014; 8: 458–466.

Turjeman

. Nano-drugs based on nano sterically stabilized liposomes for the treatment of inflammatory neurodegenerative diseases. PLoS One 2015; 10: e0130442–e0130442.

Ulmansky

Turjeman

Baru

. Glucocorticoids in nano-liposomes administered intravenously and subcutaneously to adjuvant arthritis rats are superior to the free drugs in suppressing arthritis and inflammatory cytokines. J Control Release 2012; 160: 299–305.

10.

Guo

Waknine-Grinberg

Mitchell

Barenholz

Golenser

. Reduction of experimental cerebral malaria and its related proinflammatory responses by the novel liposome-based beta-methasone nanodrug. Biomed Res Int 2014; 2014: 292471–292471.

11.

Waknine-Grinberg

Even-Chen

Avichzer

. Glucocorticosteroids in nano-sterically stabilized liposomes are efficacious for elimination of the acute symptoms of experimental cerebral malaria. PLoS One 2013; 8: e72722–e72722.

12.

Heydemann

. The super super-healing MRL mouse strain. Front Biol 2012; 7: 522–538.

13.

Perry

Sang

Yin

Zheng

Morel

. Murine models of systemic lupus erythematosus. J Biomed Biotechnol 2011; 2011: 271694–271694.

14.

Anderson

Taphouse

. Initial rate studies of hydrolysis and acyl migration in methylprednisolone 21-hemisuccinate and 17-hemisuccinate. J Pharm Sci 1981; 70: 181–186.

15.

Barenholz Y and Amselem S Quality control assays in the development and clinical use of liposome-based formulations. In: Gregoriadis G (ed.) Liposome Technology, 2nd Edn, Vol. I, Liposome Preparation and Related Techniques, Boca Raton, FL: CRC Press, 1993, pp. 527--616.

16.

Bartlett

. Phosphorus assay in column chromatography. J Biol Chem 1959; 234: 466–468.

17.

Luijten

Fritsch-Stork

Bijlsma

Derksen

. The use of glucocorticoids in systemic lupus erythematosus. After 60 years still more an art than science. Autoimmun Rev 2013; 12: 617–628.

18.

Rhen

Cidlowski

. Antiinflammatory action of glucocorticoids – new mechanisms for old drugs. N Engl J Med 2005; 353: 1711–1123–1711–1123.

19.

Schacke

Docke

Asadullah

. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther 2002; 96: 23–43.

20.

Schacke

Schottelius

Docke

. Dissociation of transactivation from transrepression by a selective glucocorticoid receptor agonist leads to separation of therapeutic effects from side effects. Proc Natl Acad Sci U S A 2004; 101: 227–232.

21.

Navarra

Guzman

Gallacher

. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: A randomised, placebo-controlled, phase 3 trial. Lancet 2011; 377: 721–731.

A liposomal steroid nano-drug for treating systemic lupus erythematosus

Abstract

Background

Objectives

Methods

Results

Conclusion

Keywords

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References