Glycol chitosan-based tacrolimus-loaded nanomicelle therapy ameliorates lupus nephritis

• Main Authors: Chang Seong Kim, Ansuja Pulickal Mathew, Arathy Vasukutty, Saji Uthaman, Soo Yeon Joo, Eun Hui Bae, Seong Kwon Ma, In-Kyu Park, Soo Wan Kim
• Format: Article
• Language: English
• Published: BMC 2021-04-01
• Series: Journal of Nanobiotechnology
• Subjects: Nanomicelles; Chitosan; Adherence; Tacrolimus; Lupus nephritis; Kidney injury
• Online Access: https://doi.org/10.1186/s12951-021-00857-w

Abstract Background Recently, we developed hydrophobically modified glycol chitosan (HGC) nanomicelles loaded with tacrolimus (TAC) (HGC-TAC) for the targeted renal delivery of TAC. Herein, we determined whether the administration of the HGC-TAC nanomicelles decreases kidney injury in a model of lupus nephritis. Lupus-prone female MRL/lpr mice were randomly assigned into three groups that received intravenous administration of either vehicle control, an equivalent dose of TAC, or HGC-TAC (0.5 mg/kg TAC) weekly for 8 weeks. Age-matched MRL/MpJ mice without Fas lpr mutation were also treated with HGC vehicle and used as healthy controls. Results Weekly intravenous treatment with HGC-TAC significantly reduced genetically attributable lupus activity in lupus nephritis-positive mice. In addition, HGC-TAC treatment mitigated renal dysfunction, proteinuria, and histological injury, including glomerular proliferative lesions and tubulointerstitial infiltration. Furthermore, HGC-TAC treatment reduced renal inflammation and inflammatory gene expression and ameliorated increased apoptosis and glomerular fibrosis. Moreover, HGC-TAC administration regulated renal injury via the TGF-β1/MAPK/NF-κB signaling pathway. These renoprotective effects of HGC-TAC treatment were more potent in lupus mice compared to those of TAC treatment alone. Conclusion Our study indicates that weekly treatment with the HGC-TAC nanomicelles reduces kidney injury resulting from lupus nephritis by preventing inflammation, fibrosis, and apoptosis. This advantage of a new therapeutic modality using kidney-targeted HGC-TAC nanocarriers may improve drug adherence and provide treatment efficacy in lupus nephritis mice.