Renal targeted delivery of triptolide by conjugation to the fragment peptide of human serum albumin |
| |
| Institution: | 1. Fondazione CEN - European Centre for Nanomedicine, Piazza Leonardo da Vinci 32, 20133 Milan, Italy;2. Dipartimento di Chimica, Materiali ed Ingegneria Chimica “G. Natta”, Politecnico di Milano, Via Mancinelli 7, 20131 Milan, Italy;3. Renal Research Laboratory, Fondazione IRCCS Ca'' Granda Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy;1. National University of Science and Technology (MISIS), Moscow 119049, Russia;2. M.V. Lomonosov Moscow State University, Moscow 119991, Russia;3. Department of Medical Nanobiotechnology, N.I Pirogov Russian National Research Medical University, Moscow 117997, Russia;4. A.N Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia;5. D. Mendeleev University of Chemical Technology of Russia, Moscow 125047, Russia |
| |
| 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-A299–585 (A299–585 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-A299–585 via a succinic acid spacer to give TPS-PF-A299–585 (TP loading 2.2% w/w). Compared with the free TP, TPS-PF-A299–585 exhibited comparable anti-inflammatory activity in the lipopolysaccharide stimulated MDCK cells, but was significantly less cytotoxic than the free drug. Accumulation of TPS-PF-A299–585 in the MDCK cells in vitro and in rodent kidneys in vivo was demonstrated using FITC-labeled TPS-PF-A299–585. 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-A299–585 was capable of alleviating the characteristic symptoms of MN. The collective data affirm PF-A299–585 to be a useful carrier for targeting TP to the kidney. |
| |
| Keywords: | Triptolide Fragment peptide Renal targeting Conjugate Human serum albumin |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
