UNIGE document Doctoral Thesis
previous document  unige:94663  next document
add to browser collection
Title

Modulation of epithelial tight junctions for barrier protection and drug delivery

Author
Directors
Defense Thèse de doctorat : Univ. Genève, 2017 - Sc. 5075 - 2017/04/28
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.
Keywords Tight junctionsDrug deliveryPenetration enhancerMucosal vaccine adjuvantAntitumor adjuvantTransmucosal permeation enhancerEpithelial barrier protection
Identifiers
URN: urn:nbn:ch:unige-946638
Full text
Thesis (2.5 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group Biopharmacie
Citation
(ISO format)
RAGUPATHY, Sakthikumar. Modulation of epithelial tight junctions for barrier protection and drug delivery. Université de Genève. Thèse, 2017. https://archive-ouverte.unige.ch/unige:94663

47 hits

1 download

Update

Deposited on : 2017-06-07

Export document
Format :
Citation style :