Conclusion
Definitely, KLPPR were able to target the diseased kidney and improve the therapeutic effect of RH on DN by exploiting the two-step nanoparticular cascade of size control and enhancement of cellular uptake. This study offers a promising strategy for renal diseases treatment using liponanoparticle delivery system.
Methods
We prepared kidney-targeted rhein (RH)-loaded liponanoparticles (KLPPR) with a yolk-shell structure composed by polycaprolactone-polyethyleneimine (PCL-PEI)-based cores and kidney targeting peptide (KTP)-modified lipid layers. The KLPPR size within the range of 30 ~ 80 nm allowed KLPPR distribute into kidney by passing through the glomerular filtration membrane and the KTP (sequence: CSAVPLC) decoration promoted the renal cellular uptake and endocytosis via a non-lysosomal pathway.
Results
The KLPPR had an average size of 59.5±6.2 nm and exhibited high RH loading, sustained release, good stability and biocompatibility, rapid cellular uptake in HK-2 cells. In addition, intravenous administration of KLPPR resulted in excellent kidney-targeted distribution and low urinary excretion in mice with streptozocin-induced diabetic nephropathy (DN), lowered the parameters of urea nitrogen, serum creatinine and kidney index, as well as facilitated the recovery of renal physiological function in improving the levels of urinary creatinine and the creatinine clearance rate by suppressing secretion and accumulation of fibronectin and TGF-β1.