Renal targeted delivery of triptolide by conjugation to the fragment peptide of human serum albumin.

Abstract We have previously demonstrated that peptide fragments (PFs) of the human serum albumin could be developed as potential renal targeting carriers, in particular, the peptide fragment, PF-A 299–585 (A 299–585 representing the amino acid sequence of the human serum albumin). In this paper, we conjugated triptolide (TP), the anti-inflammatory Chinese traditional medicine, to PF-A 299–585 via a succinic acid spacer to give TPS-PF-A 299–585 (TP loading 2.2% w/w). Compared with the free TP, TPS-PF-A 299–585 exhibited comparable anti-inflammatory activity in the lipopolysaccharide stimulated MDCK cells, but was significantly less cytotoxic than the free drug. Accumulation of TPS-PF-A 299–585 in the MDCK cells in vitro and in rodent kidneys in vivo was demonstrated using FITC-labeled TPS-PF-A 299–585 . Renal targeting was confirmed in vivo in a membranous nephropathic (MN) rodent model, where optical imaging and analyses of biochemical markers were combined to show that TPS-PF-A 299–585 was capable of alleviating the characteristic symptoms of MN. The collective data affirm PF-A 299–585 to be a useful carrier for targeting TP to the kidney.