Kidney Week

Abstract: PO1765

Glycol Chitosan-Based Tacrolimus-Loaded Nanomicelle Therapy Ameliorates Lupus Nephritis

Session Information

• Glomerular Diseases: Lupus and Membranous
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Kim, Chang Seong, Chonnam National University, Gwangju, Jeollanam-do, Korea (the Republic of)

Chang Seong Kim,

• Oh, Tae ryom, Chonnam National University, Gwangju, Jeollanam-do, Korea (the Republic of)

Tae ryom Oh,

• Choi, Hong sang, Chonnam National University, Gwangju, Jeollanam-do, Korea (the Republic of)

Hong sang Choi,

• Bae, Eun Hui, Chonnam National University, Gwangju, Jeollanam-do, Korea (the Republic of)

Eun Hui Bae,

• Ma, Seong Kwon, Chonnam National University, Gwangju, Jeollanam-do, Korea (the Republic of)

Seong Kwon Ma,

• Kim, Soo Wan, Chonnam National University, Gwangju, Jeollanam-do, Korea (the Republic of)

Soo Wan Kim,

Background

Hydrophobically modified glycol chitosan (HGC) nanomicelles loaded with tacrolimus (HGC-TAC) enhance the renal delivery of tacrolimus. Here, we determined whether the administration of HGC-TAC nanomicelles decreases kidney injury in a model of lupus nephritis.

Methods

Lupus-prone female MRL/lpr mice were randomly divided into 2 groups and given either intravenous vehicle or HGC-TAC (0.5 mg/kg tacrolimus) weekly for 8 weeks. Age-matched MRL/MpJ mice without Fas^lpr mutation were treated with a vehicle and used as healthy controls.

Results

Weekly treatment with intravenous HGC-TAC remarkably reduced genetically attributable lupus activity, blood urea nitrogen, and proteinuria in lupus nephritis-positive mice. In addition, HGC-TAC treatment mitigated renal dysfunction and histological injury, including glomerular proliferative lesions and tubulointerstitial infiltration. Furthermore, HGC-TAC treatment reduced renal inflammation and inflammatory gene expression, as well as ameliorated the increased glomerular fibrosis. Moreover, the administration of HGC-TAC appeared to regulate renal injury via the TGF-β1/p38MAPK/NF-κB signaling pathway.

Conclusion

Our study clearly indicates that weekly treatment with HGC-TAC nanomicelles reduces kidney injury resulting from lupus nephritis by preventing inflammation and fibrosis. This advantage of HGC-TAC nanocarriers may improve drug adherence and treatment efficacy in lupus nephritis patients.

Funding

• Government Support - Non-U.S.