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In vitro and in vivo assessment of delivery of hydrophobic molecules and plasmid DNAs with PEO–PPO–PEO polymeric micelles on cornea
The stability and bio-distribution of genes or drug complexes with poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO–PPO–PEO, Pluronic F-68) polymeric micelles (PM) are essential for an effective nanosized PM delivery system. We used Förster resonance energy transfer (FRET) pairs...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taiwan Food and Drug Administration
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322236/ https://www.ncbi.nlm.nih.gov/pubmed/29567259 http://dx.doi.org/10.1016/j.jfda.2017.09.002 |
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author | Hsiao, Feichin Huang, Po-Yang Aoyagi, Takao Chang, Shwu-Fen Liaw, Jiahorng |
author_facet | Hsiao, Feichin Huang, Po-Yang Aoyagi, Takao Chang, Shwu-Fen Liaw, Jiahorng |
author_sort | Hsiao, Feichin |
collection | PubMed |
description | The stability and bio-distribution of genes or drug complexes with poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO–PPO–PEO, Pluronic F-68) polymeric micelles (PM) are essential for an effective nanosized PM delivery system. We used Förster resonance energy transfer (FRET) pairs with PM and measured the FRET ratio to assess the stability of PM in vitro and in vivo on the cornea. The FRET ratio reached a plateau at 0.8 with 3% PM. Differential scanning calorimetry measurement confirmed the complex formation of FRET pairs with PM. Confocal imaging with the fluorophores fluorescein isothiocyanate isomer I (FITC) and rhodamine B base (RhB) also showed the occurrence of FRET pairs in vitro. The fluorophores were mixed with 3% PM solution or the FITC-labeled PEO–PPO–PEO polymers (FITC-P) were mixed with RhB-labeled plasmids (RhB–DNA). In addition, the in vitro corneal permeation of FRET pair complexes with PM reached a 0.8 FRET ratio. One hour after eye drop administration, FRET pairs colocalized in the cytoplasm, and surrounded and entered the nuclei of cells in the cornea, and the polymers were located in the corneal epithelial layers, as detected through anti-PEG immunohistochemistry. Furthermore, fluorescence colocalization in the cytoplasm and cell nucleus of the corneal epithelium was confirmed in tissues where RhB or RhB–DNA complexed with FITC-P was found to accumulate. We demonstrate that at a concentration of 3%, PM can encapsulate FRET pairs or RhB–DNA and retain their integrity within the cornea 1 h after administration, suggesting the feasibility and stability of PEO–PPO–PEO polymers as a vehicle for drug delivery. |
format | Online Article Text |
id | pubmed-9322236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Taiwan Food and Drug Administration |
record_format | MEDLINE/PubMed |
spelling | pubmed-93222362022-08-09 In vitro and in vivo assessment of delivery of hydrophobic molecules and plasmid DNAs with PEO–PPO–PEO polymeric micelles on cornea Hsiao, Feichin Huang, Po-Yang Aoyagi, Takao Chang, Shwu-Fen Liaw, Jiahorng J Food Drug Anal Original Article The stability and bio-distribution of genes or drug complexes with poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO–PPO–PEO, Pluronic F-68) polymeric micelles (PM) are essential for an effective nanosized PM delivery system. We used Förster resonance energy transfer (FRET) pairs with PM and measured the FRET ratio to assess the stability of PM in vitro and in vivo on the cornea. The FRET ratio reached a plateau at 0.8 with 3% PM. Differential scanning calorimetry measurement confirmed the complex formation of FRET pairs with PM. Confocal imaging with the fluorophores fluorescein isothiocyanate isomer I (FITC) and rhodamine B base (RhB) also showed the occurrence of FRET pairs in vitro. The fluorophores were mixed with 3% PM solution or the FITC-labeled PEO–PPO–PEO polymers (FITC-P) were mixed with RhB-labeled plasmids (RhB–DNA). In addition, the in vitro corneal permeation of FRET pair complexes with PM reached a 0.8 FRET ratio. One hour after eye drop administration, FRET pairs colocalized in the cytoplasm, and surrounded and entered the nuclei of cells in the cornea, and the polymers were located in the corneal epithelial layers, as detected through anti-PEG immunohistochemistry. Furthermore, fluorescence colocalization in the cytoplasm and cell nucleus of the corneal epithelium was confirmed in tissues where RhB or RhB–DNA complexed with FITC-P was found to accumulate. We demonstrate that at a concentration of 3%, PM can encapsulate FRET pairs or RhB–DNA and retain their integrity within the cornea 1 h after administration, suggesting the feasibility and stability of PEO–PPO–PEO polymers as a vehicle for drug delivery. Taiwan Food and Drug Administration 2017-11-10 /pmc/articles/PMC9322236/ /pubmed/29567259 http://dx.doi.org/10.1016/j.jfda.2017.09.002 Text en © 2018 Taiwan Food and Drug Administration https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Original Article Hsiao, Feichin Huang, Po-Yang Aoyagi, Takao Chang, Shwu-Fen Liaw, Jiahorng In vitro and in vivo assessment of delivery of hydrophobic molecules and plasmid DNAs with PEO–PPO–PEO polymeric micelles on cornea |
title | In vitro and in vivo assessment of delivery of hydrophobic molecules and plasmid DNAs with PEO–PPO–PEO polymeric micelles on cornea |
title_full | In vitro and in vivo assessment of delivery of hydrophobic molecules and plasmid DNAs with PEO–PPO–PEO polymeric micelles on cornea |
title_fullStr | In vitro and in vivo assessment of delivery of hydrophobic molecules and plasmid DNAs with PEO–PPO–PEO polymeric micelles on cornea |
title_full_unstemmed | In vitro and in vivo assessment of delivery of hydrophobic molecules and plasmid DNAs with PEO–PPO–PEO polymeric micelles on cornea |
title_short | In vitro and in vivo assessment of delivery of hydrophobic molecules and plasmid DNAs with PEO–PPO–PEO polymeric micelles on cornea |
title_sort | in vitro and in vivo assessment of delivery of hydrophobic molecules and plasmid dnas with peo–ppo–peo polymeric micelles on cornea |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322236/ https://www.ncbi.nlm.nih.gov/pubmed/29567259 http://dx.doi.org/10.1016/j.jfda.2017.09.002 |
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