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

doi:10.1002/jps.23274

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 journal › Article › peer-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 language	English (US)
Pages (from-to)	4003-4012
Number of pages	10
Journal	Journal of Pharmaceutical Sciences
Volume	101
Issue number	10
DOIs	https://doi.org/10.1002/jps.23274
State	Published - Oct 2012
Externally published	Yes

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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10.1002/jps.23274

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

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 ",

keywords = "Dextran prodrugs, Drug delivery systems, Drug targeting, Hepatic delivery, Hepatic immunosuppression, Macromolecular prodrugs, Methylprednisolone, Peptide linkers, Pharmacodynamics, Pharmacokinetics",

author = "Shaik, {Imam H.} and Agarwal, {Hitesh K.} and Keykavous Parang and Reza Mehvar",

year = "2012",

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AU - Mehvar, Reza

PY - 2012/10

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N2 - 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

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KW - Drug delivery systems

KW - Drug targeting

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KW - Hepatic immunosuppression

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KW - Peptide linkers

KW - Pharmacodynamics

KW - Pharmacokinetics

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

Abstract

Keywords

ASJC Scopus subject areas

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