Effect of surface hydrophobicity of therapeutic protein loaded in polyelectrolyte nanoparticles on transepithelial permeability
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...
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| Format: | Article |
| Language: | English |
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Sciendo
2018-09-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2018-0032 |
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| author | Miklavžin Ana Cegnar Mateja Kerč Janez Kristl Julijana |
| author_facet | Miklavžin Ana Cegnar Mateja Kerč Janez Kristl Julijana |
| author_sort | Miklavžin Ana |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ed3b06da7e684b79a16f37c7a228a69c |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2018-09-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-ed3b06da7e684b79a16f37c7a228a69c2025-02-02T09:44:23ZengSciendoActa Pharmaceutica1846-95582018-09-0168327529310.2478/acph-2018-0032acph-2018-0032Effect of surface hydrophobicity of therapeutic protein loaded in polyelectrolyte nanoparticles on transepithelial permeabilityMiklavžin Ana0Cegnar Mateja1Kerč Janez2Kristl Julijana3Faculty of Pharmacy, University of Ljubljana, SI-1000Ljubljana, SloveniaLek Pharmaceuticals d.d., Sandoz Development Center Slovenia, 1526, Ljubljana, SloveniaFaculty of Pharmacy, University of Ljubljana, SI-1000Ljubljana, SloveniaFaculty of Pharmacy, University of Ljubljana, SI-1000Ljubljana, SloveniaOral 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.https://doi.org/10.2478/acph-2018-0032erythropoietinbis-ans fluorescence intensitychitosancaco-2 modelmembrane permeabilityoral drug delivery |
| spellingShingle | Miklavžin Ana Cegnar Mateja Kerč Janez Kristl Julijana Effect of surface hydrophobicity of therapeutic protein loaded in polyelectrolyte nanoparticles on transepithelial permeability Acta Pharmaceutica erythropoietin bis-ans fluorescence intensity chitosan caco-2 model membrane permeability oral drug delivery |
| title | Effect of surface hydrophobicity of therapeutic protein loaded in polyelectrolyte nanoparticles on transepithelial permeability |
| title_full | Effect of surface hydrophobicity of therapeutic protein loaded in polyelectrolyte nanoparticles on transepithelial permeability |
| title_fullStr | Effect of surface hydrophobicity of therapeutic protein loaded in polyelectrolyte nanoparticles on transepithelial permeability |
| title_full_unstemmed | Effect of surface hydrophobicity of therapeutic protein loaded in polyelectrolyte nanoparticles on transepithelial permeability |
| title_short | Effect of surface hydrophobicity of therapeutic protein loaded in polyelectrolyte nanoparticles on transepithelial permeability |
| title_sort | effect of surface hydrophobicity of therapeutic protein loaded in polyelectrolyte nanoparticles on transepithelial permeability |
| topic | erythropoietin bis-ans fluorescence intensity chitosan caco-2 model membrane permeability oral drug delivery |
| url | https://doi.org/10.2478/acph-2018-0032 |
| work_keys_str_mv | AT miklavzinana effectofsurfacehydrophobicityoftherapeuticproteinloadedinpolyelectrolytenanoparticlesontransepithelialpermeability AT cegnarmateja effectofsurfacehydrophobicityoftherapeuticproteinloadedinpolyelectrolytenanoparticlesontransepithelialpermeability AT kercjanez effectofsurfacehydrophobicityoftherapeuticproteinloadedinpolyelectrolytenanoparticlesontransepithelialpermeability AT kristljulijana effectofsurfacehydrophobicityoftherapeuticproteinloadedinpolyelectrolytenanoparticlesontransepithelialpermeability |