en
Doctoral thesis
English

Modulation of epithelial tight junctions for barrier protection and drug delivery

Defense date2017-04-28
Abstract

We explored strategies to modulate epithelial tight junctions for barrier protection and for drug delivery. Our findings indicate that toll-like receptor 2 (TLR2) stimulation in human bronchial epithelial cells increased tight junction barrier function by increasing the expression of claudin-1, and through modulation of PKCζ activity. We designed and characterized cell permeable short peptides that can transiently open tight junctions. The peptides induced redistribution of tight junction proteins claudin-1 and ZO-1 into the intracellular compartment thereby inducing a transient increase in paracellular permeability. We investigated the lead short peptide (SG-01) for its ability to act as an anti-tumor adjuvant and mucosal vaccine adjuvant. The peptide and its combination with a cytotoxicity drug gefitinib showed a significant improvement in the reduction of tumor size in a 3D tumor model. A preclinical study in mice showed that SG-01 significantly improved immunogenicity of ovalbumin probably by improving its permeation across nasal mucosa.

eng
Keywords
  • Tight junctions
  • Drug delivery
  • Penetration enhancer
  • Mucosal vaccine adjuvant
  • Antitumor adjuvant
  • Transmucosal permeation enhancer
  • Epithelial barrier protection
Research group
Citation (ISO format)
RAGUPATHY, Sakthikumar. Modulation of epithelial tight junctions for barrier protection and drug delivery. 2017. doi: 10.13097/archive-ouverte/unige:94663
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Creation05/31/2017 11:21:00 AM
First validation05/31/2017 11:21:00 AM
Update time03/15/2023 1:44:59 AM
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