Synthesis and Evaluation of PEG-PR for Water Flux Correction in an In Situ Rat Perfusion Model
Phenol red (PR) is a widely used marker for water flux correction in studies of in situ perfusion, in which intestinal absorption usually leads to the underestimation of results. In this paper, we propose a novel marker polyethylene glycol (PEG)-PR (i.e., PR modified by PEGylation) with less permeab...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-11-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/25/21/5123 |
| _version_ | 1797548853636890624 |
|---|---|
| author | Guo Chen Xingqi Min Qunqun Zhang Zhiqiang Zhang Meiqiang Wen Jun Yang Meijuan Zou Wei Sun Gang Cheng |
| author_facet | Guo Chen Xingqi Min Qunqun Zhang Zhiqiang Zhang Meiqiang Wen Jun Yang Meijuan Zou Wei Sun Gang Cheng |
| author_sort | Guo Chen |
| collection | DOAJ |
| description | Phenol red (PR) is a widely used marker for water flux correction in studies of in situ perfusion, in which intestinal absorption usually leads to the underestimation of results. In this paper, we propose a novel marker polyethylene glycol (PEG)-PR (i.e., PR modified by PEGylation) with less permeability and evaluate its application in an in situ perfusion model in rats. PEG-PR was synthesized by the chemical conjunction of polyethylene glycol-4k/5k (PEG-4k/5k) and PR. The synthesized PEG-PR was then characterized using <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, ultraviolet (UV), X-ray diffraction (XRD), and differential scanning calorimetry (DSC) analyses. The low permeability of PEG-PR was assessed using everted gut sac (EGS) methods. The apparent permeability coefficients (<i>P</i><sub>app</sub>, 3–8 × 10<sup>−7</sup> cm/s) of PEG4k/5k-PR exhibited a nearly 15-fold reduction compared to that of PR. The different concentrations of PEG4k/5k-PR did not contribute to the <i>P</i><sub>app</sub> value or cumulative permeable percentage (about 0.02–0.06%). Furthermore, the larger molecular weight due to PEGylation (PEG5k-PR) enhanced the nonabsorbable effect. To evaluate the potential application of the novel marker, atenolol, ketoprofen, and metoprolol, which represent various biopharmaceutics classification system (BCS) classes, were selected as model drugs for the recirculation perfusion method. The water flux corrected by PEG4k/5k-PR reflected the accuracy due to the nonabsorbable effect, while the effective intestinal membrane permeability (<i>P</i><sub>eff</sub>) of atenolol corrected by PEG4k/5k-PR showed a statistically significant increase (<i>p</i> < 0.05) in different intestinal segments. In conclusion, PEG-PR is a promising marker for the permeability estimation when using the in situ perfusion model in rats. |
| first_indexed | 2024-03-10T15:05:42Z |
| format | Article |
| id | doaj.art-057f65ea5e24444ab82eb08bf39b2633 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T15:05:42Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-057f65ea5e24444ab82eb08bf39b26332023-11-20T19:43:31ZengMDPI AGMolecules1420-30492020-11-012521512310.3390/molecules25215123Synthesis and Evaluation of PEG-PR for Water Flux Correction in an In Situ Rat Perfusion ModelGuo Chen0Xingqi Min1Qunqun Zhang2Zhiqiang Zhang3Meiqiang Wen4Jun Yang5Meijuan Zou6Wei Sun7Gang Cheng8Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Biomedical Engineering, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaPhenol red (PR) is a widely used marker for water flux correction in studies of in situ perfusion, in which intestinal absorption usually leads to the underestimation of results. In this paper, we propose a novel marker polyethylene glycol (PEG)-PR (i.e., PR modified by PEGylation) with less permeability and evaluate its application in an in situ perfusion model in rats. PEG-PR was synthesized by the chemical conjunction of polyethylene glycol-4k/5k (PEG-4k/5k) and PR. The synthesized PEG-PR was then characterized using <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, ultraviolet (UV), X-ray diffraction (XRD), and differential scanning calorimetry (DSC) analyses. The low permeability of PEG-PR was assessed using everted gut sac (EGS) methods. The apparent permeability coefficients (<i>P</i><sub>app</sub>, 3–8 × 10<sup>−7</sup> cm/s) of PEG4k/5k-PR exhibited a nearly 15-fold reduction compared to that of PR. The different concentrations of PEG4k/5k-PR did not contribute to the <i>P</i><sub>app</sub> value or cumulative permeable percentage (about 0.02–0.06%). Furthermore, the larger molecular weight due to PEGylation (PEG5k-PR) enhanced the nonabsorbable effect. To evaluate the potential application of the novel marker, atenolol, ketoprofen, and metoprolol, which represent various biopharmaceutics classification system (BCS) classes, were selected as model drugs for the recirculation perfusion method. The water flux corrected by PEG4k/5k-PR reflected the accuracy due to the nonabsorbable effect, while the effective intestinal membrane permeability (<i>P</i><sub>eff</sub>) of atenolol corrected by PEG4k/5k-PR showed a statistically significant increase (<i>p</i> < 0.05) in different intestinal segments. In conclusion, PEG-PR is a promising marker for the permeability estimation when using the in situ perfusion model in rats.https://www.mdpi.com/1420-3049/25/21/5123phenol redwater flux correctionPEGylationpermeabilityeverted gut sac (EGS)in situ perfusion model |
| spellingShingle | Guo Chen Xingqi Min Qunqun Zhang Zhiqiang Zhang Meiqiang Wen Jun Yang Meijuan Zou Wei Sun Gang Cheng Synthesis and Evaluation of PEG-PR for Water Flux Correction in an In Situ Rat Perfusion Model Molecules phenol red water flux correction PEGylation permeability everted gut sac (EGS) in situ perfusion model |
| title | Synthesis and Evaluation of PEG-PR for Water Flux Correction in an In Situ Rat Perfusion Model |
| title_full | Synthesis and Evaluation of PEG-PR for Water Flux Correction in an In Situ Rat Perfusion Model |
| title_fullStr | Synthesis and Evaluation of PEG-PR for Water Flux Correction in an In Situ Rat Perfusion Model |
| title_full_unstemmed | Synthesis and Evaluation of PEG-PR for Water Flux Correction in an In Situ Rat Perfusion Model |
| title_short | Synthesis and Evaluation of PEG-PR for Water Flux Correction in an In Situ Rat Perfusion Model |
| title_sort | synthesis and evaluation of peg pr for water flux correction in an in situ rat perfusion model |
| topic | phenol red water flux correction PEGylation permeability everted gut sac (EGS) in situ perfusion model |
| url | https://www.mdpi.com/1420-3049/25/21/5123 |
| work_keys_str_mv | AT guochen synthesisandevaluationofpegprforwaterfluxcorrectioninaninsituratperfusionmodel AT xingqimin synthesisandevaluationofpegprforwaterfluxcorrectioninaninsituratperfusionmodel AT qunqunzhang synthesisandevaluationofpegprforwaterfluxcorrectioninaninsituratperfusionmodel AT zhiqiangzhang synthesisandevaluationofpegprforwaterfluxcorrectioninaninsituratperfusionmodel AT meiqiangwen synthesisandevaluationofpegprforwaterfluxcorrectioninaninsituratperfusionmodel AT junyang synthesisandevaluationofpegprforwaterfluxcorrectioninaninsituratperfusionmodel AT meijuanzou synthesisandevaluationofpegprforwaterfluxcorrectioninaninsituratperfusionmodel AT weisun synthesisandevaluationofpegprforwaterfluxcorrectioninaninsituratperfusionmodel AT gangcheng synthesisandevaluationofpegprforwaterfluxcorrectioninaninsituratperfusionmodel |