title: 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-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.
authors.affiliation: Institute of Pharmacy, Sichuan Academy of Chinese Medicine Sciences, Chengdu, Sichuan 610041, China.
authors.forename: Zhi-xiang
authors.initials: ZX
authors.lastname: Yuan
authors.affiliation: Integrative Traditional and Western Medicine Hospital of Sichuan Province, Chengdu, Sichuan 610041, China.
authors.forename: Xiao-juan
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: Pharmacy, School of Medicine and Pharmacology, The University of Western Australia, Western Australia 6009, Australia.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Mo
authors.affiliation: Department of Nutrition, Sichuan Provincial Hospital for Women and Children, Chengdu, Sichuan 610041, China.
authors.forename: Yan-li
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Institute of Pharmacy, Sichuan Academy of Chinese Medicine Sciences, Chengdu, Sichuan 610041, China. Electronic address: chaoqun_xu@sina.com.
authors.forename: Chao-qun
authors.initials: CQ
authors.lastname: Xu
authors.affiliation: Pharmacy, School of Medicine and Pharmacology, The University of Western Australia, Western Australia 6009, Australia. Electronic address: lee.lim@uwa.edu.au.
authors.forename: Lee Yong
authors.initials: LY
authors.lastname: Lim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D008516:Medicine, Chinese Traditional; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000737:chemistry*; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D004852:Epoxy Compounds; D010446:Peptide Fragments; D010616:Phenanthrenes; D012709:Serum Albumin; C001899:triptolide
keywords: Conjugate; Fragment peptide; Human serum albumin; Renal targeting; Triptolide