IL6 and TNF expression in vessels and surrounding tissues after embolization with ibuprofen-loaded beads confirms diffusion of ibuprofen

Ibuprofen from loaded embolization beads released in tissues and induced over-expression of IL6 beyond the vascular wall, in the surrounding tissues, which confirmed diffusion of the drug in a gradient of concentration. In the treatment of uterine fibroid embolization related pain, the use of emboli...

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Veröffentlicht in:European journal of pharmaceutical sciences 2011-04, Vol.42 (5), p.489-495
Hauptverfasser: Verret, Valentin, Bevilacqua, Claudia, Schwartz-Cornil, Isabelle, Pelage, Jean-Pierre, Wassef, Michel, Namur, Julien, Bédouet, Laurent, Lewis, Andrew L., Martin, Patrice, Laurent, Alexandre
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container_end_page 495
container_issue 5
container_start_page 489
container_title European journal of pharmaceutical sciences
container_volume 42
creator Verret, Valentin
Bevilacqua, Claudia
Schwartz-Cornil, Isabelle
Pelage, Jean-Pierre
Wassef, Michel
Namur, Julien
Bédouet, Laurent
Lewis, Andrew L.
Martin, Patrice
Laurent, Alexandre
description Ibuprofen from loaded embolization beads released in tissues and induced over-expression of IL6 beyond the vascular wall, in the surrounding tissues, which confirmed diffusion of the drug in a gradient of concentration. In the treatment of uterine fibroid embolization related pain, the use of embolics loaded with non-steroidal anti-inflammatory drugs (NSAID) relies on an efficient delivery and impregnation of the embolized tissue. Immuno-labelling and spectroscopic techniques have demonstrated the release of ibuprofen from drug eluting beads ( Wassef et al., 2008; Namur et al., 2009) but failed to demonstrate diffusion of the drug beyond the vascular wall (VW). We investigated whether ibuprofen diffused beyond the VW in surrounding tissues (ST), by tracking its biological effects through the modulation of expression of two main inflammatory cytokines. Uterine arteries of 6 sheep were embolized with ibuprofen loaded beads (IBU-BB) or non-loaded beads (BB) and sacrificed at one week. On frozen tissue slices, VWs of occluded arteries were isolated from ST using laser capture microdissection. RNA was extracted from VW and ST samples. Gene expression of IL6 and TNFα genes was measured by quantitative real-time PCR (qPCR). IL6 expression was significantly increased in IBU-BB compared to BB group both in VW (VW: fold-change (FC) = 4.9, p = 0.0009) and ST (ST: FC = 8.7, p = 0.0003). In IBU-BB, IL6 was significantly more expressed in VW than in ST (FC = 4.4; p = 0.0009). TNFα expression was not significantly different between IBU-BB and BB groups. Using qPCR + microdissection was useful to evaluate the spread of the biological effects of drug-loaded systems which attest of the tissular release. This approach can be considered when other drug detection techniques are unsuccessful or difficult to achieve. IL6 can be used as a marker of ibuprofen released by drug eluting beads in uterus. Gradient of expression of IL6 suggests diffusion of ibuprofen across the VW into the ST.
doi_str_mv 10.1016/j.ejps.2011.02.001
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In the treatment of uterine fibroid embolization related pain, the use of embolics loaded with non-steroidal anti-inflammatory drugs (NSAID) relies on an efficient delivery and impregnation of the embolized tissue. Immuno-labelling and spectroscopic techniques have demonstrated the release of ibuprofen from drug eluting beads ( Wassef et al., 2008; Namur et al., 2009) but failed to demonstrate diffusion of the drug beyond the vascular wall (VW). We investigated whether ibuprofen diffused beyond the VW in surrounding tissues (ST), by tracking its biological effects through the modulation of expression of two main inflammatory cytokines. Uterine arteries of 6 sheep were embolized with ibuprofen loaded beads (IBU-BB) or non-loaded beads (BB) and sacrificed at one week. On frozen tissue slices, VWs of occluded arteries were isolated from ST using laser capture microdissection. RNA was extracted from VW and ST samples. Gene expression of IL6 and TNFα genes was measured by quantitative real-time PCR (qPCR). IL6 expression was significantly increased in IBU-BB compared to BB group both in VW (VW: fold-change (FC) = 4.9, p = 0.0009) and ST (ST: FC = 8.7, p = 0.0003). In IBU-BB, IL6 was significantly more expressed in VW than in ST (FC = 4.4; p = 0.0009). TNFα expression was not significantly different between IBU-BB and BB groups. Using qPCR + microdissection was useful to evaluate the spread of the biological effects of drug-loaded systems which attest of the tissular release. This approach can be considered when other drug detection techniques are unsuccessful or difficult to achieve. IL6 can be used as a marker of ibuprofen released by drug eluting beads in uterus. 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Pharmaceutical industry ; Pharmacology. Drug treatments ; Quantitative-PCR ; Reverse Transcriptase Polymerase Chain Reaction ; Sheep ; Tissue Distribution ; Tumor Necrosis Factor-alpha - biosynthesis ; Tumor Necrosis Factor-alpha - genetics ; Uterine Artery - drug effects ; Uterine Artery - immunology ; Uterine Artery - pathology ; Uterine Artery Embolization - methods ; Uterine Neoplasms - blood supply ; Uterine Neoplasms - surgery ; Uterus - drug effects ; Uterus - immunology ; Uterus - pathology</subject><ispartof>European journal of pharmaceutical sciences, 2011-04, Vol.42 (5), p.489-495</ispartof><rights>2011 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier B.V. 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In the treatment of uterine fibroid embolization related pain, the use of embolics loaded with non-steroidal anti-inflammatory drugs (NSAID) relies on an efficient delivery and impregnation of the embolized tissue. Immuno-labelling and spectroscopic techniques have demonstrated the release of ibuprofen from drug eluting beads ( Wassef et al., 2008; Namur et al., 2009) but failed to demonstrate diffusion of the drug beyond the vascular wall (VW). We investigated whether ibuprofen diffused beyond the VW in surrounding tissues (ST), by tracking its biological effects through the modulation of expression of two main inflammatory cytokines. Uterine arteries of 6 sheep were embolized with ibuprofen loaded beads (IBU-BB) or non-loaded beads (BB) and sacrificed at one week. On frozen tissue slices, VWs of occluded arteries were isolated from ST using laser capture microdissection. RNA was extracted from VW and ST samples. Gene expression of IL6 and TNFα genes was measured by quantitative real-time PCR (qPCR). IL6 expression was significantly increased in IBU-BB compared to BB group both in VW (VW: fold-change (FC) = 4.9, p = 0.0009) and ST (ST: FC = 8.7, p = 0.0003). In IBU-BB, IL6 was significantly more expressed in VW than in ST (FC = 4.4; p = 0.0009). TNFα expression was not significantly different between IBU-BB and BB groups. Using qPCR + microdissection was useful to evaluate the spread of the biological effects of drug-loaded systems which attest of the tissular release. This approach can be considered when other drug detection techniques are unsuccessful or difficult to achieve. IL6 can be used as a marker of ibuprofen released by drug eluting beads in uterus. 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identifier ISSN: 0928-0987
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subjects Agricultural sciences
Animals
Anti-Inflammatory Agents, Non-Steroidal - administration & dosage
Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics
Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
Biological and medical sciences
Delayed-Action Preparations
Drug Delivery Systems - methods
Drug-delivery
Embolization
Female
Gene Expression - drug effects
General pharmacology
Ibuprofen
Ibuprofen - administration & dosage
Ibuprofen - pharmacokinetics
Ibuprofen - therapeutic use
IL6
Interleukin-6 - biosynthesis
Interleukin-6 - genetics
Lasers
Leiomyoma - blood supply
Leiomyoma - surgery
Life Sciences
Medical sciences
Microdissection
Microspheres
Pain, Postoperative - prevention & control
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Quantitative-PCR
Reverse Transcriptase Polymerase Chain Reaction
Sheep
Tissue Distribution
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - genetics
Uterine Artery - drug effects
Uterine Artery - immunology
Uterine Artery - pathology
Uterine Artery Embolization - methods
Uterine Neoplasms - blood supply
Uterine Neoplasms - surgery
Uterus - drug effects
Uterus - immunology
Uterus - pathology
title IL6 and TNF expression in vessels and surrounding tissues after embolization with ibuprofen-loaded beads confirms diffusion of ibuprofen
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