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The discovery of berberine erythrocyte-hemoglobin self-assembly delivery system: a neglected carrier underlying its pharmacokinetics
Berberine (BBR) has extremely low concentration and high tissue distribution. However, current pharmacokinetic studies predominantly focus on its concentration in plasma, which could hardly make a comprehensive understanding of its pharmacokinetic process. This study made a pioneering endeavor to ex...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920379/ https://www.ncbi.nlm.nih.gov/pubmed/35277093 http://dx.doi.org/10.1080/10717544.2022.2036870 |
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author | Yu, Qiuxia Li, Minhua Chen, Hanbin Xu, Lieqiang Cheng, Juanjuan Lin, Guoshu Liu, Yuhong Su, Ziren Yang, Xiaobo Li, Yucui Chen, Jiannan Xie, Jianhui |
author_facet | Yu, Qiuxia Li, Minhua Chen, Hanbin Xu, Lieqiang Cheng, Juanjuan Lin, Guoshu Liu, Yuhong Su, Ziren Yang, Xiaobo Li, Yucui Chen, Jiannan Xie, Jianhui |
author_sort | Yu, Qiuxia |
collection | PubMed |
description | Berberine (BBR) has extremely low concentration and high tissue distribution. However, current pharmacokinetic studies predominantly focus on its concentration in plasma, which could hardly make a comprehensive understanding of its pharmacokinetic process. This study made a pioneering endeavor to explore the erythrocyte-hemoglobin (Hb) self-assembly system of BBR by exploring the interaction of BBR with erythrocyte and the combination of BBR with Hb. Results showed that BBR had a low bioavailability (C(0) = 2.833 μg/mL via intravenous administration of 2.5 mg/kg BBR and C(max) = 0.260 μg/mL via oral administration of 400 mg/kg BBR). Besides, BBR achieved higher concentrations in erythrocytes than plasma, and the erythrocytes count and Hb content were significantly decreased after intravenous administration. Hemolysis rate indicated the BBR-erythrocyte system (with 2% erythrocytes) was relatively stable without hemolysis at the concentration of 1.00 mg/mL. And the maximum percentage of drug loading was 100% when the BBR-erythrocyte concentration was 0.185 μg/mL. Furthermore, incubation of BBR and erythrocytes resulted in internalization of the erythrocyte membrane and the formation of intracellular vacuoles. The thermodynamic parameters indicated that the binding process of bovine hemoglobin (BHB) and BBR was spontaneous. UV-vis absorption spectra, synchronous fluorescence, circular dichroism and Raman spectra collectively indicated that BBR showed strong binding affinity toward BHB and affected the molecular environment of residues like tryptophan and tyrosine in BHB, resulting in the conformational changes of its secondary and tertiary structure. Molecular docking indicated BBR interacted with Arg-141 residue of BHB via hydrogen bond with the bond length of 2.55 Å. The ΔG value of the BHB-BBR system was −31.79 kJ/mol. Molecular dynamics simulation indicated the root mean square derivation of BBR-BHB was <0.025 nm, suggestive of stable conformation. Cumulatively, there was an erythrocyte-Hb self-assembled drug delivery system after oral or intravenous administration of BBR, which conceivably gained novel insight into the discrepancy between the extremely low plasma concentration and relatively high tissue concentration of BBR. |
format | Online Article Text |
id | pubmed-8920379 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-89203792022-03-15 The discovery of berberine erythrocyte-hemoglobin self-assembly delivery system: a neglected carrier underlying its pharmacokinetics Yu, Qiuxia Li, Minhua Chen, Hanbin Xu, Lieqiang Cheng, Juanjuan Lin, Guoshu Liu, Yuhong Su, Ziren Yang, Xiaobo Li, Yucui Chen, Jiannan Xie, Jianhui Drug Deliv Research Article Berberine (BBR) has extremely low concentration and high tissue distribution. However, current pharmacokinetic studies predominantly focus on its concentration in plasma, which could hardly make a comprehensive understanding of its pharmacokinetic process. This study made a pioneering endeavor to explore the erythrocyte-hemoglobin (Hb) self-assembly system of BBR by exploring the interaction of BBR with erythrocyte and the combination of BBR with Hb. Results showed that BBR had a low bioavailability (C(0) = 2.833 μg/mL via intravenous administration of 2.5 mg/kg BBR and C(max) = 0.260 μg/mL via oral administration of 400 mg/kg BBR). Besides, BBR achieved higher concentrations in erythrocytes than plasma, and the erythrocytes count and Hb content were significantly decreased after intravenous administration. Hemolysis rate indicated the BBR-erythrocyte system (with 2% erythrocytes) was relatively stable without hemolysis at the concentration of 1.00 mg/mL. And the maximum percentage of drug loading was 100% when the BBR-erythrocyte concentration was 0.185 μg/mL. Furthermore, incubation of BBR and erythrocytes resulted in internalization of the erythrocyte membrane and the formation of intracellular vacuoles. The thermodynamic parameters indicated that the binding process of bovine hemoglobin (BHB) and BBR was spontaneous. UV-vis absorption spectra, synchronous fluorescence, circular dichroism and Raman spectra collectively indicated that BBR showed strong binding affinity toward BHB and affected the molecular environment of residues like tryptophan and tyrosine in BHB, resulting in the conformational changes of its secondary and tertiary structure. Molecular docking indicated BBR interacted with Arg-141 residue of BHB via hydrogen bond with the bond length of 2.55 Å. The ΔG value of the BHB-BBR system was −31.79 kJ/mol. Molecular dynamics simulation indicated the root mean square derivation of BBR-BHB was <0.025 nm, suggestive of stable conformation. Cumulatively, there was an erythrocyte-Hb self-assembled drug delivery system after oral or intravenous administration of BBR, which conceivably gained novel insight into the discrepancy between the extremely low plasma concentration and relatively high tissue concentration of BBR. Taylor & Francis 2022-03-11 /pmc/articles/PMC8920379/ /pubmed/35277093 http://dx.doi.org/10.1080/10717544.2022.2036870 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Yu, Qiuxia Li, Minhua Chen, Hanbin Xu, Lieqiang Cheng, Juanjuan Lin, Guoshu Liu, Yuhong Su, Ziren Yang, Xiaobo Li, Yucui Chen, Jiannan Xie, Jianhui The discovery of berberine erythrocyte-hemoglobin self-assembly delivery system: a neglected carrier underlying its pharmacokinetics |
title | The discovery of berberine erythrocyte-hemoglobin self-assembly delivery system: a neglected carrier underlying its pharmacokinetics |
title_full | The discovery of berberine erythrocyte-hemoglobin self-assembly delivery system: a neglected carrier underlying its pharmacokinetics |
title_fullStr | The discovery of berberine erythrocyte-hemoglobin self-assembly delivery system: a neglected carrier underlying its pharmacokinetics |
title_full_unstemmed | The discovery of berberine erythrocyte-hemoglobin self-assembly delivery system: a neglected carrier underlying its pharmacokinetics |
title_short | The discovery of berberine erythrocyte-hemoglobin self-assembly delivery system: a neglected carrier underlying its pharmacokinetics |
title_sort | discovery of berberine erythrocyte-hemoglobin self-assembly delivery system: a neglected carrier underlying its pharmacokinetics |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920379/ https://www.ncbi.nlm.nih.gov/pubmed/35277093 http://dx.doi.org/10.1080/10717544.2022.2036870 |
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