Hepatic immunosuppressive effects of systemically administered novel dextran-methylprednisolone prodrugs with peptide linkers in rats

Imam H. Shaik, Hitesh K. Agarwal, Keykavous Parang, Reza Mehvar

Research output: Contribution to journalArticlepeer-review

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 (0-2 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)-α 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-α secretion into the perfusate, with the time above the 50% inhibitory effect being

Original languageEnglish (US)
Pages (from-to)4003-4012
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume101
Issue number10
DOIs
StatePublished - Oct 2012
Externally publishedYes

Keywords

  • Dextran prodrugs
  • Drug delivery systems
  • Drug targeting
  • Hepatic delivery
  • Hepatic immunosuppression
  • Macromolecular prodrugs
  • Methylprednisolone
  • Peptide linkers
  • Pharmacodynamics
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmaceutical Science

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