PURPOSE: Zonula occludens toxin (Zot), a protein elaborated from Vibrio cholerae, has been shown to be capable of reversibly opening tight junctions. The objective of this work was to determine the stability of Zot and to examine the permeability of a series of molecular weight hydrophilic markers and therapeutic agents in the presence of Zot. METHOD: The transport of molecular weight markers (i.e., PEG 4000, FITC-dextran 10.000 and inulin) and therapeutic agents (i.e., acyclcovir, cyclopsorin, paclitaxel. doxorubicin) was evaluated with Zot (0, 2, and 4 microg/mL) using Caco-2 cell monolayers. RESULTS: Zot was found to be stable over a 10-day period. Significantly higher (p < 0.05) permeability of the molecular weight markers, in lin, and PEG4000 were observed with Zot (4 microg/mL). The transport of each therapeutic marker was significantly increased with paclitaxel displaying a >3-fold enhancement in Papp values with Zot (4 microg/mL). A 30% decrease in transepithelial electrical resistance values wa observed, which returned to baseline 30 min after Zot was removed. CONCLUSIONS: Considering the problems of poor oral bioavailability, it is concluded that Zot is a promising drug delivery technology to be used to enhance drug transport across the intestinal mucosa. Future applications are targeted at assessing its usefulness in oral drug delivery using in vivo systems.
PURPOSE: Zonula occludens toxin (Zot), a protein elaborated from Vibrio cholerae, has been shown to be capable of reversibly opening tight junctions. The objective of this work was to determine the stability of Zot and to examine the permeability of a series of molecular weight hydrophilic markers and therapeutic agents in the presence of Zot. METHOD: The transport of molecular weight markers (i.e., PEG 4000, FITC-dextran 10.000 and inulin) and therapeutic agents (i.e., acyclcovir, cyclopsorin, paclitaxel. doxorubicin) was evaluated with Zot (0, 2, and 4 microg/mL) using Caco-2 cell monolayers. RESULTS: Zot was found to be stable over a 10-day period. Significantly higher (p < 0.05) permeability of the molecular weight markers, in lin, and PEG4000 were observed with Zot (4 microg/mL). The transport of each therapeutic marker was significantly increased with paclitaxel displaying a >3-fold enhancement in Papp values with Zot (4 microg/mL). A 30% decrease in transepithelial electrical resistance values wa observed, which returned to baseline 30 min after Zot was removed. CONCLUSIONS: Considering the problems of poor oral bioavailability, it is concluded that Zot is a promising drug delivery technology to be used to enhance drug transport across the intestinal mucosa. Future applications are targeted at assessing its usefulness in oral drug delivery using in vivo systems.
Authors: A Fasano; C Fiorentini; G Donelli; S Uzzau; J B Kaper; K Margaretten; X Ding; S Guandalini; L Comstock; S E Goldblum Journal: J Clin Invest Date: 1995-08 Impact factor: 14.808
Authors: Jesica Martin; Pradeep Malreddy; Takeo Iwamoto; Lisa C Freeman; Harriet J Davidson; John M Tomich; Bruce D Schultz Journal: Invest Ophthalmol Vis Sci Date: 2009-02-21 Impact factor: 4.799