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The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization

Vesković, Ana and Nakarada, Đura and Vasiljević, Olga and Dobrov, Anatolie and Spengler, Gabriella and Enyedy, Éva Anna (2022) The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization. PHARMACEUTICS, 14 (6). ISSN 1999-4923

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Abstract

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 (HL). The binding of HL 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 HL 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 HL/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 HL 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.

Item Type: Article
Uncontrolled Keywords: cytotoxic ligand; drug release; EPR spectroscopy and imaging; HSA hydrogel; paullones; spin labeling
Subjects: Q Science / természettudomány > QD Chemistry / kémia > QD01 Analytical chemistry / analitikai kémia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 31 May 2022 08:01
Last Modified: 31 May 2022 08:01
URI: http://real.mtak.hu/id/eprint/143183

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