6 research outputs found
Colon-Targeted Cell-Permeable NFκB Inhibitory Peptide Is Orally Active against Experimental Colitis
For the purpose of development of orally active peptide
therapeutics
targeting NFκB for treatment of inflammatory bowel disease (IBD),
two major barriers in oral delivery of therapeutic peptides, metabolic
lability and tissue impermeability, were circumvented by introduction
of a colon-targeted delivery system and cell permeable peptides (CPP)
to NFκB inhibitory peptides (NIP). Suppression of NFκB
activation was compared following treatment with various CPP conjugated
NIPs (CPP–NIP). The most potent CPP–NIP was loaded in
a capsule coated with a colon specific polymer, which was administered
orally to colitic rats. The anti-inflammatory activity of the colon-targeted
CPP–NIP was evaluated by measuring inflammatory indices in
the inflamed colonic tissue. For confirmation of the local action
of the CPP–NIP, the same experiment was done after rectal administration.
Tissue permeability of the CPP–NIP was examined microscopically
and spectrophotometrically using FITC-labeled CPP–NIP (CPP–NIP-FITC).
NEMO binding domain peptide (NBD, TALDWSWLQTE) fused with a cell permeable
peptide CTP (YGRRARRRARR), CTP-NBD, was most potent in inhibiting
NFκB activity in cells. Colon-targeted CTP-NBD, but not colon-targeted
NBD and CTP-NBD in an enteric capsule, ameliorated the colonic injury,
which was in parallel with decrease in MPO activity and the levels
of inflammatory mediators. Intracolonic treatment with CTP-NBD alleviated
rat colitis and improved all the inflammatory indicators. CTP-NBD-FITC
was detected at much greater level in the inflamed tissue than was
NBD-FITC. Taken together, introduction of cell permeability and colon
targetability to NIP may be a feasible strategy for an orally active
peptide therapy for treatment of IBD
Colon-Targeted Cell-Permeable NFκB Inhibitory Peptide Is Orally Active against Experimental Colitis
For the purpose of development of orally active peptide
therapeutics
targeting NFκB for treatment of inflammatory bowel disease (IBD),
two major barriers in oral delivery of therapeutic peptides, metabolic
lability and tissue impermeability, were circumvented by introduction
of a colon-targeted delivery system and cell permeable peptides (CPP)
to NFκB inhibitory peptides (NIP). Suppression of NFκB
activation was compared following treatment with various CPP conjugated
NIPs (CPP–NIP). The most potent CPP–NIP was loaded in
a capsule coated with a colon specific polymer, which was administered
orally to colitic rats. The anti-inflammatory activity of the colon-targeted
CPP–NIP was evaluated by measuring inflammatory indices in
the inflamed colonic tissue. For confirmation of the local action
of the CPP–NIP, the same experiment was done after rectal administration.
Tissue permeability of the CPP–NIP was examined microscopically
and spectrophotometrically using FITC-labeled CPP–NIP (CPP–NIP-FITC).
NEMO binding domain peptide (NBD, TALDWSWLQTE) fused with a cell permeable
peptide CTP (YGRRARRRARR), CTP-NBD, was most potent in inhibiting
NFκB activity in cells. Colon-targeted CTP-NBD, but not colon-targeted
NBD and CTP-NBD in an enteric capsule, ameliorated the colonic injury,
which was in parallel with decrease in MPO activity and the levels
of inflammatory mediators. Intracolonic treatment with CTP-NBD alleviated
rat colitis and improved all the inflammatory indicators. CTP-NBD-FITC
was detected at much greater level in the inflamed tissue than was
NBD-FITC. Taken together, introduction of cell permeability and colon
targetability to NIP may be a feasible strategy for an orally active
peptide therapy for treatment of IBD
Colon-Targeted Cell-Permeable NFκB Inhibitory Peptide Is Orally Active against Experimental Colitis
For the purpose of development of orally active peptide
therapeutics
targeting NFκB for treatment of inflammatory bowel disease (IBD),
two major barriers in oral delivery of therapeutic peptides, metabolic
lability and tissue impermeability, were circumvented by introduction
of a colon-targeted delivery system and cell permeable peptides (CPP)
to NFκB inhibitory peptides (NIP). Suppression of NFκB
activation was compared following treatment with various CPP conjugated
NIPs (CPP–NIP). The most potent CPP–NIP was loaded in
a capsule coated with a colon specific polymer, which was administered
orally to colitic rats. The anti-inflammatory activity of the colon-targeted
CPP–NIP was evaluated by measuring inflammatory indices in
the inflamed colonic tissue. For confirmation of the local action
of the CPP–NIP, the same experiment was done after rectal administration.
Tissue permeability of the CPP–NIP was examined microscopically
and spectrophotometrically using FITC-labeled CPP–NIP (CPP–NIP-FITC).
NEMO binding domain peptide (NBD, TALDWSWLQTE) fused with a cell permeable
peptide CTP (YGRRARRRARR), CTP-NBD, was most potent in inhibiting
NFκB activity in cells. Colon-targeted CTP-NBD, but not colon-targeted
NBD and CTP-NBD in an enteric capsule, ameliorated the colonic injury,
which was in parallel with decrease in MPO activity and the levels
of inflammatory mediators. Intracolonic treatment with CTP-NBD alleviated
rat colitis and improved all the inflammatory indicators. CTP-NBD-FITC
was detected at much greater level in the inflamed tissue than was
NBD-FITC. Taken together, introduction of cell permeability and colon
targetability to NIP may be a feasible strategy for an orally active
peptide therapy for treatment of IBD
Colon-Targeted Cell-Permeable NFκB Inhibitory Peptide Is Orally Active against Experimental Colitis
For the purpose of development of orally active peptide
therapeutics
targeting NFκB for treatment of inflammatory bowel disease (IBD),
two major barriers in oral delivery of therapeutic peptides, metabolic
lability and tissue impermeability, were circumvented by introduction
of a colon-targeted delivery system and cell permeable peptides (CPP)
to NFκB inhibitory peptides (NIP). Suppression of NFκB
activation was compared following treatment with various CPP conjugated
NIPs (CPP–NIP). The most potent CPP–NIP was loaded in
a capsule coated with a colon specific polymer, which was administered
orally to colitic rats. The anti-inflammatory activity of the colon-targeted
CPP–NIP was evaluated by measuring inflammatory indices in
the inflamed colonic tissue. For confirmation of the local action
of the CPP–NIP, the same experiment was done after rectal administration.
Tissue permeability of the CPP–NIP was examined microscopically
and spectrophotometrically using FITC-labeled CPP–NIP (CPP–NIP-FITC).
NEMO binding domain peptide (NBD, TALDWSWLQTE) fused with a cell permeable
peptide CTP (YGRRARRRARR), CTP-NBD, was most potent in inhibiting
NFκB activity in cells. Colon-targeted CTP-NBD, but not colon-targeted
NBD and CTP-NBD in an enteric capsule, ameliorated the colonic injury,
which was in parallel with decrease in MPO activity and the levels
of inflammatory mediators. Intracolonic treatment with CTP-NBD alleviated
rat colitis and improved all the inflammatory indicators. CTP-NBD-FITC
was detected at much greater level in the inflamed tissue than was
NBD-FITC. Taken together, introduction of cell permeability and colon
targetability to NIP may be a feasible strategy for an orally active
peptide therapy for treatment of IBD
Colon-Targeted Cell-Permeable NFκB Inhibitory Peptide Is Orally Active against Experimental Colitis
For the purpose of development of orally active peptide
therapeutics
targeting NFκB for treatment of inflammatory bowel disease (IBD),
two major barriers in oral delivery of therapeutic peptides, metabolic
lability and tissue impermeability, were circumvented by introduction
of a colon-targeted delivery system and cell permeable peptides (CPP)
to NFκB inhibitory peptides (NIP). Suppression of NFκB
activation was compared following treatment with various CPP conjugated
NIPs (CPP–NIP). The most potent CPP–NIP was loaded in
a capsule coated with a colon specific polymer, which was administered
orally to colitic rats. The anti-inflammatory activity of the colon-targeted
CPP–NIP was evaluated by measuring inflammatory indices in
the inflamed colonic tissue. For confirmation of the local action
of the CPP–NIP, the same experiment was done after rectal administration.
Tissue permeability of the CPP–NIP was examined microscopically
and spectrophotometrically using FITC-labeled CPP–NIP (CPP–NIP-FITC).
NEMO binding domain peptide (NBD, TALDWSWLQTE) fused with a cell permeable
peptide CTP (YGRRARRRARR), CTP-NBD, was most potent in inhibiting
NFκB activity in cells. Colon-targeted CTP-NBD, but not colon-targeted
NBD and CTP-NBD in an enteric capsule, ameliorated the colonic injury,
which was in parallel with decrease in MPO activity and the levels
of inflammatory mediators. Intracolonic treatment with CTP-NBD alleviated
rat colitis and improved all the inflammatory indicators. CTP-NBD-FITC
was detected at much greater level in the inflamed tissue than was
NBD-FITC. Taken together, introduction of cell permeability and colon
targetability to NIP may be a feasible strategy for an orally active
peptide therapy for treatment of IBD
Colon-Targeted Cell-Permeable NFκB Inhibitory Peptide Is Orally Active against Experimental Colitis
For the purpose of development of orally active peptide
therapeutics
targeting NFκB for treatment of inflammatory bowel disease (IBD),
two major barriers in oral delivery of therapeutic peptides, metabolic
lability and tissue impermeability, were circumvented by introduction
of a colon-targeted delivery system and cell permeable peptides (CPP)
to NFκB inhibitory peptides (NIP). Suppression of NFκB
activation was compared following treatment with various CPP conjugated
NIPs (CPP–NIP). The most potent CPP–NIP was loaded in
a capsule coated with a colon specific polymer, which was administered
orally to colitic rats. The anti-inflammatory activity of the colon-targeted
CPP–NIP was evaluated by measuring inflammatory indices in
the inflamed colonic tissue. For confirmation of the local action
of the CPP–NIP, the same experiment was done after rectal administration.
Tissue permeability of the CPP–NIP was examined microscopically
and spectrophotometrically using FITC-labeled CPP–NIP (CPP–NIP-FITC).
NEMO binding domain peptide (NBD, TALDWSWLQTE) fused with a cell permeable
peptide CTP (YGRRARRRARR), CTP-NBD, was most potent in inhibiting
NFκB activity in cells. Colon-targeted CTP-NBD, but not colon-targeted
NBD and CTP-NBD in an enteric capsule, ameliorated the colonic injury,
which was in parallel with decrease in MPO activity and the levels
of inflammatory mediators. Intracolonic treatment with CTP-NBD alleviated
rat colitis and improved all the inflammatory indicators. CTP-NBD-FITC
was detected at much greater level in the inflamed tissue than was
NBD-FITC. Taken together, introduction of cell permeability and colon
targetability to NIP may be a feasible strategy for an orally active
peptide therapy for treatment of IBD