title: Synthesis, characterization and in vitro evaluation of triptolide-lysozyme conjugate for renal targeting delivery of triptolide.
abstract: A triptolide-lysozyme (TP-LZM) conjugate was synthesized to achieve renal specific delivery and to reduce the side effects of triptolide. Triptolide was coupled to lysozyme through succinic via an ester bond with an average coupling degree of 1 mol triptolide per 1 mol lysozyme. The lysozyme can specifically accumulate in the proximal tubular cells of the kidney, making it a potential carrier for targeting drugs to the kidney. The structure of triptolide succinate (TPS) was confirmed by IR, 1H-NMR, MS and UV. The concentrations of triptolide in various samples were determined by reversed-phase high-performance liquid chromatography (HPLC). In this study, the physicochemical and stability profiles of TP-LZM under various conditions were investgated the stability and releasing profiles of triptolide-lysozyme (TP-LZM) under various conditions. In vitro release trails showed triptolide-lysozyme was relatively stable in plasma (less than 30% of free triptolide released) and could release triptolide quickly in lysosome (more than 80% of free triptolide released) at 37 degrees C for 24 h. In addition, the biological activities of the conjugate on normal rat kidney proximal tubular cells (NRK52E) were also tested. The conjugate can effectively reduce NO production in the medium of NRK52E induced by lipopolysaccharide (LPS) but with much lower toxicity. These studies suggest the possibility to promote curative effect and reduce its extra-renal toxicity of triptolide by TP-LZM conjugate.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Ministry of Education, West China School of Pharmacy, Sichuan University, Sichuan 610041, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zheng
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D004224:Diterpenes / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry*; D016503:Drug Delivery Systems; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D010616:Phenanthrenes; C001899:triptolide; D009569:Nitric Oxide; D009113:Muramidase