title: Prednisolone-glucose derivative conjugate: synthesis, biodistribution and pharmacodynamics evaluation.
abstract: This study was aimed at synthesizing and evaluating a prednisolone-glucose derivative conjugate (PDG) that was expected to increase renal biodistribution without affecting pharmacological action and to decrease the systemic side effects of prednisolone. The PDG was designed and synthesized by tethering 6-amino-6-deoxy-D-glucose (a D-glucose derivative) to prednisolone and its chemical structure was confirmed by (1) H NMR, (13) C NMR, and LC-MS. This conjugate was then subjected to in vitro and in vivo evaluation like stability studies, biological distribution, pharmacodynamics, and systemic side effects studies. In these studies, PDG not only showed significant enhancement of renal target efficiency with high values of relative uptake efficiency (RE, 24.1), concentration efficiency (CE, 8.6), and kidney targeting index (KTI, 16.3), but retained the curative potency against minimal change nephrosis (MCN). In the systemic side effects study, no osteoporosis was observed in rats after the administration of PDG for 20 days, which exhibited limited side effects. Conclusively, our findings showed a pharmacologically active conjugate with the characteristics of renal targeting and limited systemic side effects. The results implied the potential of PDG as a promising therapeutic in the treatment of renal diseases.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Wenhao
authors.initials: W
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liang
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Yangming
authors.initials: Y
authors.lastname: Guo
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D004355:Drug Stability; D005938:Glucocorticoids / Q000009:adverse effects / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D005947:Glucose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D009401:Nephrosis / Q000097:blood / Q000188:drug therapy / Q000652:urine; D009928:Organ Specificity; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D005938:Glucocorticoids; D011239:Prednisolone; D005947:Glucose