{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T14:10:01Z","timestamp":1774275001028,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773673"],"award-info":[{"award-number":["81773673"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"\u201cPioneer\u201d and \u201cLeading Goose\u201d R&D Program of Zhejiang","award":["2024C03107"],"award-info":[{"award-number":["2024C03107"]}]},{"name":"\u201cPioneer\u201d and \u201cLeading Goose\u201d R&D Program of Zhejiang","award":["2025C02254(SD2)"],"award-info":[{"award-number":["2025C02254(SD2)"]}]},{"name":"Joint TCM Science & Technology Projects of National Demonstration Zones for Comprehensive TCM Reform","award":["GZY-KJS-ZJ-2025-081"],"award-info":[{"award-number":["GZY-KJS-ZJ-2025-081"]}]},{"name":"Zhejiang Province Traditional Chinese Medicine Science and Technology Project","award":["2024ZL857"],"award-info":[{"award-number":["2024ZL857"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), characterized by immune system disorders and multiple organ damage. Current clinical treatment of LN requires a complex multi-drug combination, which is often associated with severe side effects and low patient compliance. The aim of this study was to design a self-nanoemulsifying drug delivery system (SNEDDS) co-loading total glucosides of Paeonia (TGP) and dihydroartemisinin (DHA) to increase the solubility of the drug as well as achieve synergistic anti-inflammatory and immunomodulatory effects for LN therapy. Network pharmacology, molecular docking and molecular dynamics simulations were employed to predict the core therapeutic targets and related signaling pathways. The SNEDDS co-loaded with TGP and DHA was optimized via central composite design response surface methodology (CCD-RSM). Its physicochemical properties, particle size and the polydispersity index (PDI) of the optimized formulation were characterized. In vivo therapeutic efficacy was evaluated in MRL\/lpr mice by measuring disease-related indicators (urinary protein, serum ANA, and anti-ds-DNA) and inflammatory cytokines (TNF-\u03b1, IL-6, and IL-1\u03b2). Renal tissue pathology was also examined. All data were analyzed by one-way analysis of variance (ANOVA) with p &lt; 0.05 considered statistically significant. The core therapeutic targets predicted with high relevance were AKT1, MAPK1, MAPK3, and RELA. The optimized SNEDDS achieved a high loading capacity of 16.11 \u00b1 0.43 mg\/g for TGP and 12.79 \u00b1 1.33 mg\/g for DHA, with a particle size of (25.84 \u00b1 0.30) nm and PDI of (0.07 \u00b1 0.02). In MRL\/lpr mice, SNEDDS treatment significantly reduced urinary protein levels (p &lt; 0.01), serum ANA (p &lt; 0.01) and anti-ds-DNA titers (p &lt; 0.01) compared with the model group. Additionally, the levels of pro-inflammatory cytokines (TNF-\u03b1, IL-6, and IL-1\u03b2) were markedly decreased (p &lt; 0.05), and renal tissue damage was alleviated. Conclusions: The SNEDDS co-loaded TGP and DHA is a promising oral nanotherapeutic strategy for LN, offering synergistic anti-inflammatory and immunomodulatory effects.<\/jats:p>","DOI":"10.3390\/biom16030476","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:07:06Z","timestamp":1774271226000},"page":"476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Drug Delivery System for the Treatment of Lupus Nephritis: From Delivery System Design and Optimization to Treatment"],"prefix":"10.3390","volume":"16","author":[{"given":"Xumeng","family":"Xiong","sequence":"first","affiliation":[{"name":"Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo 315302, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zhejiang Pharmaceutical University, Ningbo 315100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zequn","family":"Jin","sequence":"additional","affiliation":[{"name":"College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7755-6192","authenticated-orcid":false,"given":"Ying","family":"Hu","sequence":"additional","affiliation":[{"name":"Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo 315302, China"},{"name":"School of Pharmacy, Zhejiang Pharmaceutical University, Ningbo 315100, China"},{"name":"College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.2215\/CJN.01280122","article-title":"Short- and Long-Term Progression of Kidney Involvement in Systemic Lupus Erythematosus Patients with Low-Grade Proteinuria","volume":"17","author":"Wang","year":"2022","journal-title":"Clin. 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