Poly-γ-glutamic acid coating polymeric nanoparticles enhance renal drug distribution and cellular uptake for diabetic nephropathy therapy

Abstract

Poor drug distribution and inefficient renal cellular uptake are the major barriers diminishing the efficacy of nanoparticles in renal targeted therapy. We designed the rhein (RH)-loaded poly-γ-glutamic acid (PGA)-coated polycaprolactone-polyethyleneimine nanoparticles (RGPP) to enhance renal drug distribution and cellular uptake via PGA-mediated receptor-ligand interaction with γ-glutamyltranspeptidase (GGT) expressed highly in the kidney. PGA coating not only ensured the stability, sustained drug release, and biocompatibility of RGPP, but also promoted renal cellular uptake via binding with the GGT on the renal cells. Following intravenous administration, PGA coating protects RGPP from recognition by the reticuloendothelial system, resulting in prolonged blood circulation. RGPP enables targeted RH accumulation in the kidneys of streptozotocin-induced diabetic nephropathy (DN) mice, resulting in significant recovery of renal physiological function. The PGA coating strategy opens a new avenue for the management of renal diseases using nanomedicine.

Keywords:

• Diabetic nephropathy
• poly-γ-glutamic acid
• rhein
• kidney-targeted drug delivery
• nanoparticles

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No. 82102191), the Science and Technology Program on Traditional Chinese Medicine of Zhejiang Province (No. 2019ZA059, 2020ZB084), Science and Technology Program on Medicine and Health of Zhejiang Province (No. 2022KY913).