A highly potent lymphatic system-targeting nanoparticle cyclosporine prevents glomerulonephritis in mouse model of lupus.

Abstract:

:Cyclosporine A (CsA) is a powerful immunosuppressant, but it is an ineffective stand-alone treatment for systemic lupus erythematosus (SLE) due to poor target tissue distribution and renal toxicity. We hypothesized that CD71 (transferrin receptor 1)-directed delivery of CsA to the lymphatic system would improve SLE outcomes in a murine model. We synthesized biodegradable, ligand-conjugated nanoparticles [P2Ns-gambogic acid (GA)] targeting CD71. GA conjugation substantially increased nanoparticle association with CD3+ or CD20+ lymphocytes and with intestinal lymphoid tissues. In orally dosed MRL-lpr mice, P2Ns-GA-encapsulated CsA increased lymphatic drug delivery 4- to 18-fold over the ligand-free formulation and a commercial CsA capsule, respectively. Improved lymphatic bioavailability of CsA was paralleled by normalization of anti-double-stranded DNA immunoglobulin G titer, plasma cytokines, and glomerulonephritis. Thus, this study demonstrates the translational potential of nanoparticles that enhance the targeting of lymphatic tissues, transforming CsA into a potent single therapeutic for SLE.

journal_name

Sci Adv

journal_title

Science advances

authors

Ganugula R,Arora M,Zou D,Agarwal SK,Mohan C,Kumar MNVR

doi

10.1126/sciadv.abb3900

subject

Has Abstract

pub_date

2020-06-12 00:00:00

pages

eabb3900

issue

24

issn

2375-2548

pii

abb3900

journal_volume

6

pub_type

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