title: Effects of mycophenolic acid-glucosamine conjugates on the base of kidney targeted drug delivery.
abstract: Mycophenolic acid has played an important role in treating immunosuppression and autoimmune diseases. Nevertheless, the agent needs a high dosage in treatment, following some side effects. To tackle this problem, in this study, mycophenolic acid-glucosamine conjugate (MGC), modified by 2-glucosamine, was synthesized to achieve kidney targeting and improved drug efficacy with a lower dosage. (1)H NMR, (13)C NMR and HRMS spectroscopy were used to verify the conjugate whose stability was good in vitro. The transport of MGC by human proximal renal tubular epithelial HK-2 cells was temperature-, time-, concentration-dependent and saturable, suggesting the involvement of carrier-mediated uptake. In addition, the cellular uptake of MGC dropped substantially with the inhibition of megalin receptor. The specific tissue distribution indicated the commendable renal-targeting capability of MGC. The concentration of MGC was improved in the kidney except for other tissues, about 6.76 times higher than that of MPA. Further, the bioavailability of MGC in plasma decreased as compared with mycophenolic acid. Moreover, therapeutic effect of MGC was enhanced significantly compared with MPA in the acute kidney injury model. All the findings suggested the potential of mycophenolic acid-glucosamine conjugate in kidney targeted drug delivery.
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Southern Renmin Road, No. 17, Section 3, Chengdu 610041, PR China.
authors: Xiaohong
authors: X
authors: Wang
authors: Yan
authors: Y
authors: Lin
authors: Yingchun
authors: Y
authors: Zeng
authors: Xun
authors: X
authors: Sun
authors: Tao
authors: T
authors: Gong
authors: Zhirong
authors: Z
authors: Zhang
mesh_terms: D000818:Animals; D001682:Biological Availability; D001806:Blood Urea Nitrogen; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D016503:Drug Delivery Systems; D005944:Glucosamine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D014018:Tissue Distribution
chemical_list: D003404:Creatinine; D009173:Mycophenolic Acid; D005944:Glucosamine
keywords: 2-Glucosamine; 4-dimethylamiopryidine; BUN; CKD; CREA; Chronic kidney diseases; DCC; DCM; DMAP; DMF; Drug delivery; EDTA; I/R; Kidney targeting; LMWC; MGC; MMF; MPA; Mycophenolic acid; N,N-Dimethylformamide; blood urea nitrogen; chronic kidney disease; dichloromethane; dicyclohexylcarbodiimide; ethylene diamine tetraacetic acid; ischemia-reperfusion; low molecular weight chitosan; mycophenolate mofetil; mycophenolic acid; mycophenolic acid–glucosamine conjugate; serum creatine