Document Type
Article
Publication Date
2012
Abstract
The hepatic immunosuppressive activities of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP1) or five (DMP5) amino acids as linkers were studied in rats. At various times (02 weeks) after intravenous administration of single 5 mg/kg (MP equivalent) doses of each prodrug or MP succinate (MPS), livers were isolated and immunologically stimulated ex vivo with lipopolysaccharide. The concentrations of tumor necrosis factor (TNF)-a in the outlet perfusate were then quantitated to assess immune response. Additionally, the concentrations of DMP1, DMP5, and/or MP were measured in the liver. MPS, DMP5, or DMP1 injections caused a maximum of 48.9%, 63.5%, or 85.7% decrease in the TNF-a secretion into the perfusate, with the time above the 50% inhibitory effect being <5, <24, or 120 h, respectively. Additionally, the area under the effecttime curve for DMP1 was 11-fold or fourfold higher than that after the administration of MPS or DMP5, respectively. Relatively high concentrations of DMP1 were present in the liver even at the last sampling time of 2 weeks. These data suggest that a single intravenous dose of DMP1 produces an intense and sustained immunosuppression in the liver for a relatively long time, which may be useful in liver transplantation.
Recommended Citation
Shaik, Imam H., Hitesh K. Agarwal, Keykavous Parang, and Reza Mehvar. "Hepatic immunosuppressive effects of systemically administered novel dextran–methylprednisolone prodrugs with peptide linkers in rats." Journal of pharmaceutical sciences 101, no. 10 (2012): 4003-4012.
DOI:10.1002/jps.23274
Copyright
Wiley
Included in
Amino Acids, Peptides, and Proteins Commons, Animals Commons, Immune System Diseases Commons, Pharmaceutics and Drug Design Commons
Comments
This is the accepted version of the following article:
Shaik, Imam H., Hitesh K. Agarwal, Keykavous Parang, and Reza Mehvar. "Hepatic immunosuppressive effects of systemically administered novel dextran–methylprednisolone prodrugs with peptide linkers in rats." Journal of pharmaceutical sciences 101, no. 10 (2012): 4003-4012.
which has been published in final form at DOI: 10.1002/jps.23274.