Free radicals generated by tantalum implants antagonize the cytotoxic effect of doxorubicin

TY - JOUR

T1 - Free radicals generated by tantalum implants antagonize the cytotoxic effect of doxorubicin

AU - Chen, Muwan

AU - Hein, San

AU - Le, Dang Q S

AU - Feng, Wenzhou

AU - Foss, Morten

AU - Kjems, Jørgen

AU - Besenbacher, Flemming

AU - Zou, Xuenong

AU - Bünger, Cody

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013

Y1 - 2013

N2 - Little is known about the interaction between antineoplastic drugs and implants in bone cancer patients. We investigated the interaction between commercially available porous tantalum (Ta) implants and the chemotherapeutic drug, Doxorubicin (DOX). DOX solutions were prepared in the presence of Ta implant. The changes in fluorescence intensity of the DOX chromophore were measured by spectrofluorometry and the efficacy of DOX was evaluated by viability of rabbit rectal tumor cells (VX2). After 5 min interaction of the DOX solution (5 μg/ml) with the Ta implant, the fluorescent intensity of the DOX solution was 85% degraded, and only 20% the drug efficacy to kill VX2 cells was retained. However, after adding a reducing agent, Dithiothreitol (DTT, 10 μg/ml), 80% of the original fluorescence and 50% of the drug efficacy were restored while UV irradiation enhanced drug degradation in the presence of Ta implant. The action of DTT and UV irradiation indicated that reactive oxygen species (ROS) were involved in the drug degradation mechanism. We detected that Ta implants in aqueous medium produced hydroxyl radicals. Cells showed higher intracellular ROS activity when culture medium was incubated with the Ta implant prior to cell culture. It is concluded that the porous Ta implant antagonizes the cytotoxicity of DOX via ROS generation of the porous Ta implant.

AB - Little is known about the interaction between antineoplastic drugs and implants in bone cancer patients. We investigated the interaction between commercially available porous tantalum (Ta) implants and the chemotherapeutic drug, Doxorubicin (DOX). DOX solutions were prepared in the presence of Ta implant. The changes in fluorescence intensity of the DOX chromophore were measured by spectrofluorometry and the efficacy of DOX was evaluated by viability of rabbit rectal tumor cells (VX2). After 5 min interaction of the DOX solution (5 μg/ml) with the Ta implant, the fluorescent intensity of the DOX solution was 85% degraded, and only 20% the drug efficacy to kill VX2 cells was retained. However, after adding a reducing agent, Dithiothreitol (DTT, 10 μg/ml), 80% of the original fluorescence and 50% of the drug efficacy were restored while UV irradiation enhanced drug degradation in the presence of Ta implant. The action of DTT and UV irradiation indicated that reactive oxygen species (ROS) were involved in the drug degradation mechanism. We detected that Ta implants in aqueous medium produced hydroxyl radicals. Cells showed higher intracellular ROS activity when culture medium was incubated with the Ta implant prior to cell culture. It is concluded that the porous Ta implant antagonizes the cytotoxicity of DOX via ROS generation of the porous Ta implant.

KW - Animals

KW - Antibiotics, Antineoplastic

KW - Cell Line, Tumor

KW - Cell Survival

KW - Dithiothreitol

KW - Doxorubicin

KW - Prostheses and Implants

KW - Rabbits

KW - Reactive Oxygen Species

KW - Tantalum

KW - Ultraviolet Rays

U2 - 10.1016/j.ijpharm.2013.03.041

DO - 10.1016/j.ijpharm.2013.03.041

M3 - Journal article

C2 - 23538094

SN - 0378-5173

VL - 448

SP - 214

EP - 220

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 1

ER -