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Modulation of epithelial tight junctions for barrier protection and drug delivery

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
URN: urn:nbn:ch:unige-946638
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Research group Biopharmacie
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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

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Deposited on : 2017-06-07

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