Chellappan, D. R. | bioRxiv Science

bioRxiv2026

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

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.

physiology↗

bioRxiv2025

Customized feminine hygiene wash containing postbiotics from Lactobacillus spp. to treat Urinary Tract Infections (UTI)

The rising prevalence of antimicrobial resistance has intensified the search for innovative therapeutic strategies, particularly in the prevention of urinary tract infections (UTIs). This study presents the development and evaluation of a novel postbiotics vaginal wash formulated to prevent UTIs by utilizing metabolites derived from indigenous vaginal Lactobacillus spp. The primary objective was to create a cost-effective, stable, and non-invasive solution targeting uropathogenic bacteria. Key metabolites, including tryptamine, (-)-terpinen-4-ol, and itaconic anhydride, were identified from cell free supernatant of vaginal Lactobacillus and incorporated into a poloxamer 407-based formulation. In vitro assays demonstrated significant bioactivity against uropathogenic bacteria, effectively inhibiting bacterial colonization and biofilm formation. Preclinical validation was conducted using BALB/c mice models to assess both the safety and efficacy of the vaginal wash. Results indicated a substantial reduction in infection rates among treated mice, with no observed adverse effects, confirming the formulations safety profile. In conclusion, this novel postbiotics vaginal wash represents a promising non-invasive therapeutic approach for UTI prevention. By harnessing bioactive metabolites from human vaginal Lactobacillus spp., the formulation offers a potential solution to combat antimicrobial resistance while improving womens health outcomes. Further clinical studies are warranted to validate these findings and explore broader applications in clinical practice, paving the way for new strategies in managing UTIs and enhancing overall female health.

microbiology↗