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In vitro characterization of immune modulating drug-eluting immunobeads towards transarterial embolization in cancer

Hepatocellular carcinoma (HCC) is an aggressive liver cancer with limited effective treatment options. In this study, we selected TLR agonists imiquimod (IMQ), gardiquimod (GARD), GS-9620 and DSR 6434, and a small molecule checkpoint inhibitor, BMS-202, for characterization of drug loading and relea...

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Published in:Scientific reports 2022-12, Vol.12 (1), p.21886-11, Article 21886
Main Authors: Negussie, Ayele H., Mikhail, Andrew S., Owen, Joshua W., Hong, Natalie, Carlson, Camella J., Tang, Yiqing, Carrow, Kendal Paige, Mauda-Havakuk, Michal, Lewis, Andrew L., Karanian, John W., Pritchard, William F., Wood, Bradford J.
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creator Negussie, Ayele H.
Mikhail, Andrew S.
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Lewis, Andrew L.
Karanian, John W.
Pritchard, William F.
Wood, Bradford J.
description Hepatocellular carcinoma (HCC) is an aggressive liver cancer with limited effective treatment options. In this study, we selected TLR agonists imiquimod (IMQ), gardiquimod (GARD), GS-9620 and DSR 6434, and a small molecule checkpoint inhibitor, BMS-202, for characterization of drug loading and release from radiopaque embolic beads (DC Bead LUMI) for potential use in image-guided transarterial embolization (TACE) of HCC. The maximum drug loading capacity and amount of drug released over time were determined by high performance liquid chromatography and compared with the commonly used anthracycline, doxorubicin hydrochloride (Dox). Maximum drug loading was 204.54 ± 3.87, 65.97 ± 1.54, 65.95 ± 6.96, 65.28 ± 3.09, and 148.05 ± 2.24 mg of drug per milliliter of DC Bead LUMI for Dox, GARD, DSR 6434, IMQ, and BMS-202, respectively. Fast loading and subsequent rapid release in saline were observed for IMQ, GARD, and DSR 6434. These drugs could also be partially removed from the beads by repeated washing with de-ionized water suggesting weak interaction with the beads. Aggregation of IMQ was observed in water and saline. GS-9620 partially decomposed in the solubilizing solution, so loading and release were not characterized. Compared to TLR agonists, slower loading and release were observed for Dox and BMS-202. Potential factors influencing drug loading into and release from DC Bead LUMI including steric hinderance, hydrophobicity, drug pKa, and the electrostatic nature of the beads are discussed. The maximum loading capacity of BMS-202 and Dox in DC Bead LUMI exceeded the maximum theoretical loading capacity of the beads expected from ionic interaction alone suggesting additional drug-bead or drug-drug interactions may play a role. Slightly more release was observed for BMS-202 at early time points followed by a slower release compared to Dox. Further study of these drug-bead combinations is warranted in search of new tools for locoregional delivery of immune-modulating agents for treatment of HCC via drug-eluting bead chemoembolization.
doi_str_mv 10.1038/s41598-022-26094-1
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In this study, we selected TLR agonists imiquimod (IMQ), gardiquimod (GARD), GS-9620 and DSR 6434, and a small molecule checkpoint inhibitor, BMS-202, for characterization of drug loading and release from radiopaque embolic beads (DC Bead LUMI) for potential use in image-guided transarterial embolization (TACE) of HCC. The maximum drug loading capacity and amount of drug released over time were determined by high performance liquid chromatography and compared with the commonly used anthracycline, doxorubicin hydrochloride (Dox). Maximum drug loading was 204.54 ± 3.87, 65.97 ± 1.54, 65.95 ± 6.96, 65.28 ± 3.09, and 148.05 ± 2.24 mg of drug per milliliter of DC Bead LUMI for Dox, GARD, DSR 6434, IMQ, and BMS-202, respectively. Fast loading and subsequent rapid release in saline were observed for IMQ, GARD, and DSR 6434. These drugs could also be partially removed from the beads by repeated washing with de-ionized water suggesting weak interaction with the beads. Aggregation of IMQ was observed in water and saline. GS-9620 partially decomposed in the solubilizing solution, so loading and release were not characterized. Compared to TLR agonists, slower loading and release were observed for Dox and BMS-202. Potential factors influencing drug loading into and release from DC Bead LUMI including steric hinderance, hydrophobicity, drug pKa, and the electrostatic nature of the beads are discussed. The maximum loading capacity of BMS-202 and Dox in DC Bead LUMI exceeded the maximum theoretical loading capacity of the beads expected from ionic interaction alone suggesting additional drug-bead or drug-drug interactions may play a role. Slightly more release was observed for BMS-202 at early time points followed by a slower release compared to Dox. 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subjects 631/250
631/67
639/638
Agonists
Anthracycline
Antibiotics, Antineoplastic - chemistry
Carcinoma, Hepatocellular - therapy
Chemoembolization, Therapeutic - methods
Doxorubicin
Doxorubicin - chemistry
Drug delivery
Embolization
Hepatocellular carcinoma
High-performance liquid chromatography
Humanities and Social Sciences
Humans
Hydrophobicity
Imiquimod
Immune checkpoint inhibitors
Immunomodulation
Immunosuppressive agents
Liquid chromatography
Liver cancer
Liver Neoplasms - therapy
Microspheres
multidisciplinary
Science
Science (multidisciplinary)
title In vitro characterization of immune modulating drug-eluting immunobeads towards transarterial embolization in cancer
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