ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 636

Liposomal-Glucocorticoids: A Novel Approach to the Therapy of SLE

Yaakov Naparstek1, Eli Moallem2, Rina Ulmansky3, Erez Koren3 and Yechezkel Barenholz3, 1Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel, 2Dept. of Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel, 3Hadassah - Hebrew University Medical Center, Jerusalem, Israel

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Title: Systemic Lupus Erythematosus - Animal Models

Session Type: Abstract Submissions (ACR)

Background/Purpose

Glucocorticoids (GCs) have been known for years to be the most effective therapy in SLE. Their use is however limited by the need of high doses due to the unfavorable pharmacokinetics and biodistribution of the drug. A possible approach to overcome this obstacle is to use liposomal formulation that has a different biodistribution than that of the free GCs. We have previously developed a new liposomal GC formulation and demonstrated its specific accumulation in inflamed tissues, as well as superior therapeutic efficacy over that of free GC in the autoimmune adjuvant arthritis model. In the present study we have tested the effect of the liposomal GC formulation in the murine SLE model of MRL/lpr/lpr mice.

Methods

We used 80 nm sterically stabilized nanoliposomes which were remote-loaded with an amphipathic weak acid GC methylprednisolone hemisuccinate (liposomal GC). Six-weeks old MRL/lpr/lpr mice were injected subcutaneously with either the liposomal GC 25 mg/kg weekly, or free MPS 5 mg/kg daily, or the appropriate solvents and their clinical course, kidney damage and serology, followed until the age of 24 weeks.

Results

No mortality was observed in mice treated with the liposomal GC up to 24 weeks, as compared to 20% and 30% mortality in the free MPS and the solvent-treated groups. Anti-dsDNA levels (OD) were 0.49±0.05 in the liposomal GC group, compared to 1.21±0.22 and 1.7±0.12 in the two other groups. Significant reduction of spleen size was observed in the liposomal GC-treated group, 1.09±0.43 cm2, compared to 2.98±0.65 cm2 and 2.82±0.51 cm2 in the two other groups. A significant improvement in renal histopathology was achieved in the liposomal GC treatment, and mean urea levels were 8.8±1.05 nM/L in the liposomal GC group compared to 18.9±3.86 nM/L and 22.5±2.69 nM/L in the two other groups.

Conclusion

Liposomal GC has significant superiority over daily injections of free MPS in suppressing murine lupus. These results make our liposomal GC formulation a good candidate for the treatment of human SLE.

Disclosure:

Y. Naparstek,
None;

E. Moallem,
None;

R. Ulmansky,
None;

E. Koren,
None;

Y. Barenholz,
None.

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