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bioRxiv · 10.64898/2026.08.01.742194

Glomerular-Targeted Delivery of Low-Dose Prednisolone Attenuates Established Lupus Nephritis in MRL/lpr Mice.

Williams, K.·Agyekum, G.·Patne, A.·Markoutsa, E.·Chellappan, D. R.·Hall, N.·Tian, Z.·Hernandez Soto, N.·Cuadrao, S.·Lozonschi, I.·Fu, L.·Haight, L.·Sharma, R.·Mohapatra, S.·Wang, L.·Mohapatra, S. S.·Liu, R.
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Abstract

BackgroundLupus nephritis remains a major cause of chronic kidney disease and kidney failure in systemic lupus erythematosus. Glucocorticoids are central to treatment but are limited by systemic toxicity. We evaluated whether a previously characterized collagen IV 3-targeted liposomal nanoparticle formulation carrying low-dose prednisolone could attenuate established lupus nephritis in MRL/lpr mice. MethodsFemale MRL/lpr mice with disease present at treatment initiation and C57BL/6J control mice received saline or collagen IV 3-targeted prednisolone-loaded nanoparticles (Col4-3-Pred-NPs). Renal outcomes were assessed by longitudinal proteinuria, glomerular filtration rate (GFR), survival, kidney histopathology, renal IgG and C3d deposition, dUTP/TUNEL-associated injury staining, and renal cytokine/chemokine profiling. Body weight, food and water intake, and blood glucose were monitored as measures of general condition and preliminary tolerability. ResultsCol4-3-Pred-NPs improved survival in MRL/lpr mice, reduced cumulative proteinuria burden, and attenuated terminal GFR decline compared with saline-treated MRL/lpr controls. Treatment reduced glomerular and tubulointerstitial injury, lowered composite EGTI histopathology scores, decreased terminal kidney enlargement, reduced glomerular IgG deposition and renal dUTP-positive injury signals, and reduced renal signals for IL-28A/B, IL-7, PD-ECGF, IL-11, CCL6/C10, and IL-15. C3d deposition was not significantly altered. Nanoparticle treatment was not associated with sustained treatment-related increases in blood glucose or body-weight loss during the measured study period. ConclusionsCollagen IV 3-targeted liposomal delivery of low-dose prednisolone attenuated established lupus nephritis in MRL/lpr mice and improved renal structural, functional, inflammatory, and survival outcomes. These findings support further evaluation of glomerulus-targeted nanotherapy as a potential strategy to improve the precision and therapeutic index of glucocorticoid treatment in lupus nephritis.

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Williams, K., Agyekum, G., Patne, A., Markoutsa, E., Chellappan, D. R., Hall, N., Tian, Z., Hernandez Soto, N., Cuadrao, S., Lozonschi, I., Fu, L., Haight, L., Sharma, R., Mohapatra, S., Wang, L., Mohapatra, S. S., Liu, R.. 2026-08-06. Glomerular-Targeted Delivery of Low-Dose Prednisolone Attenuates Established Lupus Nephritis in MRL/lpr Mice.. https://doi.org/10.64898/2026.08.01.742194

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