Evaluation of 3-Borono-<span style="font-variant: small-caps">l</span>-Phenylalanine as a Water-Soluble Boron Neutron Capture Therapy Agent
Although 4-borono-<span style="font-variant: small-caps;">l</span>-phenylalanine (4-BPA) is currently the only marketed agent available for boron neutron capture therapy (BNCT), its low water solubility raises concerns. In this study, we synthesized 3-borono-<span style=&quo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/5/1106 |
| _version_ | 1797496482070265856 |
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| author | Naoya Kondo Fuko Hirano Takashi Temma |
| author_facet | Naoya Kondo Fuko Hirano Takashi Temma |
| author_sort | Naoya Kondo |
| collection | DOAJ |
| description | Although 4-borono-<span style="font-variant: small-caps;">l</span>-phenylalanine (4-BPA) is currently the only marketed agent available for boron neutron capture therapy (BNCT), its low water solubility raises concerns. In this study, we synthesized 3-borono-<span style="font-variant: small-caps;">l</span>-phenylalanine (3-BPA), a positional isomer of 4-BPA, with improved water solubility. We further evaluated its physicochemical properties, tumor accumulation, and biodistribution. The water solubility of 3-BPA was 125 g/L, which is more than 100 times higher than that of 4-BPA. Due to the high water solubility, we prepared the administration solution of 3-BPA without a solubilizer sugar, which is inevitably added to 4-BPA preparation and has adverse effects. In in vitro and in vivo experiments, boron accumulation in cancers after administration was statistically equivalent in both sugar-complexed 3-BPA and 4-BPA. Furthermore, the biodistribution of 3-BPA was comparable with that of sugar-complexed 3-BPA. Since 3-BPA has high water solubility and tumor targetability equivalent to 4-BPA, 3-BPA can replace 4-BPA in future BNCT. |
| first_indexed | 2024-03-10T03:05:14Z |
| format | Article |
| id | doaj.art-01b34d0780f84685a0d64e3b210f42ed |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:05:14Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-01b34d0780f84685a0d64e3b210f42ed2023-11-23T12:39:43ZengMDPI AGPharmaceutics1999-49232022-05-01145110610.3390/pharmaceutics14051106Evaluation of 3-Borono-<span style="font-variant: small-caps">l</span>-Phenylalanine as a Water-Soluble Boron Neutron Capture Therapy AgentNaoya Kondo0Fuko Hirano1Takashi Temma2Department of Biofunctional Analysis, Graduate School of Pharmaceutical Sciences, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki 569-1094, Osaka, JapanDepartment of Biofunctional Analysis, Graduate School of Pharmaceutical Sciences, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki 569-1094, Osaka, JapanDepartment of Biofunctional Analysis, Graduate School of Pharmaceutical Sciences, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki 569-1094, Osaka, JapanAlthough 4-borono-<span style="font-variant: small-caps;">l</span>-phenylalanine (4-BPA) is currently the only marketed agent available for boron neutron capture therapy (BNCT), its low water solubility raises concerns. In this study, we synthesized 3-borono-<span style="font-variant: small-caps;">l</span>-phenylalanine (3-BPA), a positional isomer of 4-BPA, with improved water solubility. We further evaluated its physicochemical properties, tumor accumulation, and biodistribution. The water solubility of 3-BPA was 125 g/L, which is more than 100 times higher than that of 4-BPA. Due to the high water solubility, we prepared the administration solution of 3-BPA without a solubilizer sugar, which is inevitably added to 4-BPA preparation and has adverse effects. In in vitro and in vivo experiments, boron accumulation in cancers after administration was statistically equivalent in both sugar-complexed 3-BPA and 4-BPA. Furthermore, the biodistribution of 3-BPA was comparable with that of sugar-complexed 3-BPA. Since 3-BPA has high water solubility and tumor targetability equivalent to 4-BPA, 3-BPA can replace 4-BPA in future BNCT.https://www.mdpi.com/1999-4923/14/5/1106boron neutron capture therapy4-borono-<span style="font-variant: small-caps">l</span>-phenylalaninedrug discoverysolubility |
| spellingShingle | Naoya Kondo Fuko Hirano Takashi Temma Evaluation of 3-Borono-<span style="font-variant: small-caps">l</span>-Phenylalanine as a Water-Soluble Boron Neutron Capture Therapy Agent Pharmaceutics boron neutron capture therapy 4-borono-<span style="font-variant: small-caps">l</span>-phenylalanine drug discovery solubility |
| title | Evaluation of 3-Borono-<span style="font-variant: small-caps">l</span>-Phenylalanine as a Water-Soluble Boron Neutron Capture Therapy Agent |
| title_full | Evaluation of 3-Borono-<span style="font-variant: small-caps">l</span>-Phenylalanine as a Water-Soluble Boron Neutron Capture Therapy Agent |
| title_fullStr | Evaluation of 3-Borono-<span style="font-variant: small-caps">l</span>-Phenylalanine as a Water-Soluble Boron Neutron Capture Therapy Agent |
| title_full_unstemmed | Evaluation of 3-Borono-<span style="font-variant: small-caps">l</span>-Phenylalanine as a Water-Soluble Boron Neutron Capture Therapy Agent |
| title_short | Evaluation of 3-Borono-<span style="font-variant: small-caps">l</span>-Phenylalanine as a Water-Soluble Boron Neutron Capture Therapy Agent |
| title_sort | evaluation of 3 borono span style font variant small caps l span phenylalanine as a water soluble boron neutron capture therapy agent |
| topic | boron neutron capture therapy 4-borono-<span style="font-variant: small-caps">l</span>-phenylalanine drug discovery solubility |
| url | https://www.mdpi.com/1999-4923/14/5/1106 |
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