The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization
This study shows the potential of a thermally induced human serum albumin (HSA) hydrogel to serve as a drug depot for sustained release of a highly cytotoxic modified paullone ligand bearing a TEMPO free radical (<b>HL</b>). The binding of <b>HL</b> to HSA was studied by elec...
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| Format: | Article |
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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/1999-4923/14/6/1174 |
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| author | Ana Vesković Đura Nakarada Olga Vasiljević Anatolie Dobrov Gabriella Spengler Éva A. Enyedy Vladimir B. Arion Ana Popović Bijelić |
| author_facet | Ana Vesković Đura Nakarada Olga Vasiljević Anatolie Dobrov Gabriella Spengler Éva A. Enyedy Vladimir B. Arion Ana Popović Bijelić |
| author_sort | Ana Vesković |
| collection | DOAJ |
| description | This study shows the potential of a thermally induced human serum albumin (HSA) hydrogel to serve as a drug depot for sustained release of a highly cytotoxic modified paullone ligand bearing a TEMPO free radical (<b>HL</b>). The binding of <b>HL</b> to HSA was studied by electron paramagnetic resonance (EPR) spectroscopy and imaging. The EPR protocol was also implemented for the study of matrix degradation, and ligand diffusion rate, in two additional spin-labeled hydrogels, containing 5-doxylstearate and 3-carbamoyl-proxyl. The results showed that the hydrogel is an efficient <b>HL</b> reservoir as it retained 60% of the ligand during 11 days of dialysis in physiological saline. Furthermore, upon incubation with Colo 205 human colon adenocarcinoma cells for 3 days, the <b>HL</b>/HSA hydrogel did not exhibit cytotoxic activity, demonstrating that it is also an efficient ligand depot in the presence of living cells. It was observed that the percentage of <b>HL</b> release is independent of its initial concentration in the hydrogel, suggesting that HSA possesses a specific binding site for the ligand, most likely Sudlow site 2, as predicted by molecular docking. The intrinsic property of albumin to bind and transport various substances, including hydrophobic drugs, may be fine-tuned by appropriate physical/chemical hydrogel preparation procedures, providing optimal drug delivery. |
| first_indexed | 2024-03-09T22:45:15Z |
| format | Article |
| id | doaj.art-2dbfda08494d472b84e5da357737470a |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T22:45:15Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2dbfda08494d472b84e5da357737470a2023-11-23T18:29:27ZengMDPI AGPharmaceutics1999-49232022-05-01146117410.3390/pharmaceutics14061174The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic CharacterizationAna Vesković0Đura Nakarada1Olga Vasiljević2Anatolie Dobrov3Gabriella Spengler4Éva A. Enyedy5Vladimir B. Arion6Ana Popović Bijelić7Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11158 Belgrade, SerbiaFaculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11158 Belgrade, SerbiaFaculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11158 Belgrade, SerbiaInstitute of Inorganic Chemistry, University of Vienna, Währinger Strasse 42, A-1090 Vienna, AustriaMTA-SZTE Lendület Functional Metal Complexes Research Group, Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, HungaryMTA-SZTE Lendület Functional Metal Complexes Research Group, Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, HungaryInstitute of Inorganic Chemistry, University of Vienna, Währinger Strasse 42, A-1090 Vienna, AustriaFaculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11158 Belgrade, SerbiaThis study shows the potential of a thermally induced human serum albumin (HSA) hydrogel to serve as a drug depot for sustained release of a highly cytotoxic modified paullone ligand bearing a TEMPO free radical (<b>HL</b>). The binding of <b>HL</b> to HSA was studied by electron paramagnetic resonance (EPR) spectroscopy and imaging. The EPR protocol was also implemented for the study of matrix degradation, and ligand diffusion rate, in two additional spin-labeled hydrogels, containing 5-doxylstearate and 3-carbamoyl-proxyl. The results showed that the hydrogel is an efficient <b>HL</b> reservoir as it retained 60% of the ligand during 11 days of dialysis in physiological saline. Furthermore, upon incubation with Colo 205 human colon adenocarcinoma cells for 3 days, the <b>HL</b>/HSA hydrogel did not exhibit cytotoxic activity, demonstrating that it is also an efficient ligand depot in the presence of living cells. It was observed that the percentage of <b>HL</b> release is independent of its initial concentration in the hydrogel, suggesting that HSA possesses a specific binding site for the ligand, most likely Sudlow site 2, as predicted by molecular docking. The intrinsic property of albumin to bind and transport various substances, including hydrophobic drugs, may be fine-tuned by appropriate physical/chemical hydrogel preparation procedures, providing optimal drug delivery.https://www.mdpi.com/1999-4923/14/6/1174cytotoxic liganddrug releaseEPR spectroscopy and imagingHSA hydrogelpaullonesspin labeling |
| spellingShingle | Ana Vesković Đura Nakarada Olga Vasiljević Anatolie Dobrov Gabriella Spengler Éva A. Enyedy Vladimir B. Arion Ana Popović Bijelić The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization Pharmaceutics cytotoxic ligand drug release EPR spectroscopy and imaging HSA hydrogel paullones spin labeling |
| title | The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization |
| title_full | The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization |
| title_fullStr | The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization |
| title_full_unstemmed | The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization |
| title_short | The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization |
| title_sort | release of a highly cytotoxic paullone bearing a tempo free radical from the hsa hydrogel an epr spectroscopic characterization |
| topic | cytotoxic ligand drug release EPR spectroscopy and imaging HSA hydrogel paullones spin labeling |
| url | https://www.mdpi.com/1999-4923/14/6/1174 |
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