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Prednisolone‐Glucose Derivative Conjugate: Synthesis, Biodistribution and Pharmacodynamics Evaluation
Author(s) -
Liu Xing,
Li Wenhao,
Liang Zhen,
Zhang Xuan,
Guo Yangming,
Gong Tao,
Zhang Zhirong
Publication year - 2012
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201200232
Subject(s) - biodistribution , conjugate , prednisolone , pharmacology , chemistry , pharmacodynamics , in vivo , potency , bioavailability , distribution (mathematics) , nephrosis , kidney , therapeutic index , pharmacokinetics , medicine , endocrinology , in vitro , drug , biochemistry , biology , mathematical analysis , mathematics , microbiology and biotechnology
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.