<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Oral delivery of protein drugs is greatly limited by low hydrophobicity, an important determinant for intestinal epithelial permeation and bioavailability. Herein, surface properties of recombinant erythropoietin were investigated using the fluorescent dye bis-ANS to monitor relative hydrophobicity for correlation with permeabilities with Caco-2 cells. At various pHs, bis-ANS fluorescence intensity indicated different surface hydrophobicities of erythropoietin molecules. Erythropoietin incorporated in chitosan or chitosan-trimethylchitosan (CS-TMC) nanoparticles prepared by polyelectrolyte complexation and ionotropic gelation with tripolyphosphate also showed different surface hydrophobicities. Chitosan nanoparticles with erythropoietin provided the most hydrophobic surface, followed by free erythropoietin (in water) and that loaded into CS-TMC nanoparticles. Chitosan nanoparticles were more effective than CS-TMC nanoparticles for permeation of erythropoietin across Caco-2 cell monolayers; the lowest permeability was shown by erythropoietin itself. Thus, hydrophilic protein molecules complexed with polyelectrolytes can provide more hydrophobic surfaces that enhance transepithelial permeability. This bis-ANS method also provides valuable information for the design of polyelectrolyte nanoparticules for oral delivery of protein drugs.</p></abstract>

Oral delivery of protein drugs is greatly limited by low hydrophobicity, an important determinant for intestinal epithelial permeation and bioavailability. Herein, surface properties of recombinant erythropoietin were investigated using the fluorescent dye bis-ANS to monitor relative hydrophobicity for correlation with permeabilities with Caco-2 cells. At various pHs, bis-ANS fluorescence intensity indicated different surface hydrophobicities of erythropoietin molecules. Erythropoietin incorporated in chitosan or chitosan-trimethylchitosan (CS-TMC) nanoparticles prepared by polyelectrolyte complexation and ionotropic gelation with tripolyphosphate also showed different surface hydrophobicities. Chitosan nanoparticles with erythropoietin provided the most hydrophobic surface, followed by free erythropoietin (in water) and that loaded into CS-TMC nanoparticles. Chitosan nanoparticles were more effective than CS-TMC nanoparticles for permeation of erythropoietin across Caco-2 cell monolayers; the lowest permeability was shown by erythropoietin itself. Thus, hydrophilic protein molecules complexed with polyelectrolytes can provide more hydrophobic surfaces that enhance transepithelial permeability. This bis-ANS method also provides valuable information for the design of polyelectrolyte nanoparticules for oral delivery of protein drugs.

Effect of surface hydrophobicity of therapeutic protein loaded in polyelectrolyte nanoparticles on transepithelial permeability

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Oral delivery of protein drugs is greatly limited by low hydrophobicity, an important determinant for intestinal epithelial permeation and bioavailability....

Effect of surface hydrophobicity of therapeutic protein loaded in polyelectrolyte nanoparticles on transepithelial permeability

Published Online: Jul 04, 2018

Page range: 275 - 293

Accepted: May 25, 2018

DOI: https://doi.org/10.2478/acph-2018-0032

Keywords
erythropoietin, bis-ANS fluorescence intensity, chitosan, Caco-2 model, membrane permeability, oral drug delivery

© 2018 Ana Miklavžin et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Effect of surface hydrophobicity of therapeutic protein loaded in polyelectrolyte nanoparticles on transepithelial permeability

Published Online: Jul 04, 2018

Page range: 275 - 293

Accepted: May 25, 2018

DOI: https://doi.org/10.2478/acph-2018-0032

Keywordserythropoietin, bis-ANS fluorescence intensity, chitosan, Caco-2 model, membrane permeability, oral drug delivery

© 2018 Ana Miklavžin et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
erythropoietin, bis-ANS fluorescence intensity, chitosan, Caco-2 model, membrane permeability, oral drug delivery