title: Targeted drug delivery to renal proximal tubule epithelial cells mediated by 2-glucosamine.
abstract: In order to develop a novel kidney-targeted drug delivery system, we synthesized prednisolone carbamate-glucosamine conjugate (PCG) using 2-glucosamine as a ligand, and investigated its potential targeting efficacy. In vitro studies demonstrated that PCG could remarkably improve the uptake of drug by kidney cells. And the specific uptake of PCG could be largely reduced by the inhibitors of megalin receptor. More importantly, PCG showed an excellent kidney targeting property in vivo, and the concentration of the conjugate in the kidney was 8.1-fold higher than that of prednisolone group at 60 min after intravenous injection. Besides, PCG could significantly reverse the disease progression in renal ischemia-reperfusion (I/R) injury animal models. Furthermore, PCG presented no adverse effect on bone density while prednisolone resulted in severe osteoporosis. Thus, it indicated that 2-glucosamine could be a potential ligand for kidney-targeted delivery of prednisolone.
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, Sichuan, People's Republic of China.
authors: Yan
authors: Y
authors: Lin
authors: Yanping
authors: Y
authors: Li
authors: Xiaohong
authors: X
authors: Wang
authors: Tao
authors: T
authors: Gong
authors: Ling
authors: L
authors: Zhang
authors: Xun
authors: X
authors: Sun
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D015519:Bone Density / Q000187:drug effects; D002219:Carbamates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism*; D005944:Glucosamine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution
chemical_list: D000893:Anti-Inflammatory Agents; D002219:Carbamates; D011239:Prednisolone; D005944:Glucosamine