References of "Drion, Pierre"
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See detailDUSP3 Phosphatase Deficiency or Inhibition Limit Platelet Activation and Arterial Thrombosis
Musumeci, Lucia ULg; Kuijpers, Marijke; Gilio, Karen et al

in Circulation (in press)

Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet ... [more ▼]

Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet activation is of importance for the development of improved therapies. Recently, protein tyrosine phosphatases (PTPs) have emerged as critical regulators of platelet function. Methods and Results This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion mediated through the collagen receptor glycoprotein VI (GPVI) and the C-type lectin-like receptor 2 (CLEC-2). DUSP3-deficient mice were more resistant to collagen- and epinephrine-induced thromboembolism, compared to wild-type mice, and showed severely impaired thrombus formation upon ferric chloride-induced carotid artery injury. Intriguingly, bleeding times were not altered in DUSP3-deficient mice. At the molecular level, DUSP3 deficiency impaired Syk tyrosine phosphorylation, subsequently reducing phosphorylation of PLCγ2 and calcium fluxes. To investigate DUSP3 function in human platelets, a novel small-molecule inhibitor of DUSP3 was developed. This compound specifically inhibited collagen and CLEC-2-induced human platelet aggregation, thereby phenocopying the effect of DUSP3 deficiency in murine cells. Conclusions DUSP3 plays a selective and essential role in collagen- and CLEC-2-mediated platelet activation and thrombus formation in vivo. Inhibition of DUSP3 may prove therapeutic for arterial thrombosis. This is the first time a PTP, implicated in platelet signaling, has been targeted with a small-molecule drug. [less ▲]

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See detailPlasma riche en plaquettes et lésions tendineuses
KAUX, Jean-François ULg; Drion, Pierre ULg; Croisier, Jean-Louis ULg et al

in Revue Médicale de Liège (2014), 69(Synthèse 2014), 67-72

Platelets contain growth factors released during their degranulation following activation. These growth factors promote tissue remodeling, wound healing and angiogenesis. Currently, the clinical effect of ... [more ▼]

Platelets contain growth factors released during their degranulation following activation. These growth factors promote tissue remodeling, wound healing and angiogenesis. Currently, the clinical effect of Platelet-Rich Plasma (PRP) is still discussed or even controversial. Our researches have evaluated the effectiveness of PRP on the healing of animal tendons and human suffering from chronic jumper's knee. [less ▲]

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See detailInfusion of clinical-grade enriched regulatory T cells delays experimental xenogeneic graft-versus-host disease
Hannon, Muriel ULg; LECHANTEUR, Chantal ULg; Lucas, Sophie et al

in Transfusion (2014), 54(February), 353-363

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See detailEccentric training improves tendon biomechanical properties: a rat model
Kaux, Jean-François ULg; Drion, Pierre ULg; Libertiaux, Vincent et al

in British Journal of Sports Medicine (2014, April), 48(7), 155

Background: Even if eccentric exercises appear favourable in primary prevention of tendons lesions and, especially, in secondary prevention after tendinopathy, the biomechanical changes to the tissue are ... [more ▼]

Background: Even if eccentric exercises appear favourable in primary prevention of tendons lesions and, especially, in secondary prevention after tendinopathy, the biomechanical changes to the tissue are not yet clear. Objective: We aimed to better define the biomechanical changes that affect healthy tendon after eccentric and concentric training. Design: Randomised controlled trial. Participants: Eighteen Sprague-Dawley rats of 2 months. Interventions: The six rats in the control group (U) were not subjected to physical exercise. The 12 remaining rats (6 in each group) ran on a treadmill set at a +15° incline for concentric training (C) or a -15° incline for eccentric training (E), at a speed of 17 m/min for 1 h, three times per week for 5 weeks. Main Outcome Measurements: The tricipital, patellar and Achilles tendons were subsequently removed to perform a traction test until rupture, and a histological analysis was performed. Results: There was a significant improvement in the rupture force of the patellar and tricipital tendons between the U and E groups. The tricipital tendons in the control group presented a significantly smaller cross-section than the E- and C-trained groups, but none between E and C groups. No significant difference was observed for the mechanical stress at rupture per surface unit between the three groups for all three tendons. However, a tendency towards improvement these values was observed between the trained and the U groups for the patellar tendon. Histological studies demonstrated the tendency of the development of a greater number of blood vessels and a larger quantity of collagen in the eccentric group. Conclusions: The mechanical properties of tendons in rats improve after specific training, especially following eccentric training. Our results partly explained how mechanical loading, especially in eccentric mode, could improve the tendon structure. [less ▲]

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See detailDUSP3/VHR is a pro-angiogenic atypical dual-specificity phosphatase
Amand, Mathieu ULg; Erpicum, Charlotte ULg; BAJOU, Khalid ULg et al

Poster (2014, January 27)

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See detailCryopreservation of embryos : a way to reduce the number of housed animals and the genetic drift.
Remy, Benoît ULg; Ectors, Fabien ULg; Drion, Pierre ULg

Poster (2014, January 27)

The GIGA Mouse facility platform has recently improved its mouse line cryopreservation technique. The method of embryo cryopreservation by rapid cooling also called aseptic vitrification has been selected ... [more ▼]

The GIGA Mouse facility platform has recently improved its mouse line cryopreservation technique. The method of embryo cryopreservation by rapid cooling also called aseptic vitrification has been selected. Vitrification media, key steps and timing have been optimized and validated. After a first partial exposition of the embryos to cryoprotective solutions, they are immersed in a vitrifying mixture of penetrating and non-penetrating cryoprotectants for a short time. The straw containing the embryos is immediately sealed before to be plunged in LN2, resulting in a brutal solidification in which crystallization does not have time to occur. [less ▲]

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See detailGIGA ANIMAL CARE : Mice & Zebrafish Animal Facility and Transgenesis
Remy, Benoît ULg; Ectors, Fabien ULg; Winandy, Marie ULg et al

Poster (2014, January 27)

In fundamental research, animal models allow to place molecular and cellular observations back into their physiological context. In applied research, these models still remain a mandatory step to evaluate ... [more ▼]

In fundamental research, animal models allow to place molecular and cellular observations back into their physiological context. In applied research, these models still remain a mandatory step to evaluate the efficiency and the toxicity of potential treatments, before going to clinical trials. Mouse and Zebrafish (Danio rerio) are two very interesting models because of a short live cycle and a high prolificacy. They require a limited space. Their genome is well known and shows a high homology with the human. Many tools are available to produce transgenic mice or zebrafishes. Many tests are validated using both these species. [less ▲]

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See detailImmunomodulatory effects of Rapamycin in xenogeneic GVHD
Ehx, Grégory ULg; HANNON, Muriel ULg; DUBOIS, Sophie ULg et al

Poster (2014, January 27)

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See detailVascular Endothelial Growth Factor-111 (VEGF-111) and tendon healing: preliminary results in a rat model of tendon injury
Kaux, Jean-François ULg; Janssen, Lauriane ULg; Drion, Pierre ULg et al

in Muscles, Ligaments and Tendons Journal (2014), 4(1), 25-28

Tendon lesions are among the most frequent musculoskeletal pathologies. Vascular endothelial growth factor (VEGF) is known to regulate angiogenesis. VEGF-111, a biologically active and proteolysis ... [more ▼]

Tendon lesions are among the most frequent musculoskeletal pathologies. Vascular endothelial growth factor (VEGF) is known to regulate angiogenesis. VEGF-111, a biologically active and proteolysis-resistant splice variant of this family, was recently identified. This study aimed at evaluating whether VEGF-111 could have a therapeutic interest in tendon pathologies. Surgical section of one Achilles tendon of rats was performed before a local injection of either saline or VEGF-111. After 5, 15 and 30 days, the Achilles tendons of 10 rats of both groups were sampled and submitted to a biomechanical tensile test. The force necessary to induce tendon rupture was greater for tendons of the VEGF-111 group (p<0.05) while the section areas of the tendons were similar. The mechanical stress was similar at 5 and 15 days in the both groups but was improved for the VEGF-111 group at day 30 (p <0.001). No difference was observed in the mRNA expression of collagen III, tenomodulin and MMP-9. In conclusion, we observed that a local injection of VEGF-111 improves the early phases of the healing process of rat tendons after a surgical section. Further confirmatory experimentations are needed to consolidate our results. [less ▲]

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See detailEstablishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation
Binsfeld, Marilène ULg; Beguin, Yves ULg; Belle, Ludovic et al

in PLoS ONE (2014), (doi:10.1371), 113764

Background: Multiple myeloma (MM) is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM) effects, the use of allogeneic ... [more ▼]

Background: Multiple myeloma (MM) is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM) effects, the use of allogeneic hematopoietic stem cell transplantation (allo-SCT) has remained controversial in MM. In the current study, we investigated the anti-myeloma effects of allo-SCT from B10.D2 mice into MHC-matched myeloma-bearing Balb/cJ mice (previously injected with the MOPC315.BM myeloma cell line), based on a chronic graft-versus-host disease (GvHD) murine model. Methods and results: Balb/cJ mice were injected intravenously with luciferase-transfected MOPC315.BM cells, and received 30 days later an allogeneic (B10.D2 donor) or autologous (Balb/cJ donor) transplantation by intravenous administration of bone marrow cells and splenocytes. We observed a graft-versus-myeloma effect in 94% of the allogeneic transplanted mice, as luciferase signal completely disappeared after transplantation, whereas all the autologous transplanted mice showed myeloma evolution. Lower serum paraprotein levels and myeloma infiltration in bone marrow and spleen in the allogeneic setting confirmed the observed GvM effect, while allogeneic mice also displayed chronic GvHD symptoms. In vivo and in vitro data suggest the involvement of effector memory CD4 and CD8 T cells in the GvM effect. The essential role of CD8 T cells was demonstrated in vivo where CD8 T-cell depletion of the graft resulted in reduced GvM effects. Finally, TCR V spectratyping analysis identified V families within CD4 and CD8 T cells which were associated with both GvM effects and GVHD, whereas other V families within CD4 T cells were associated exclusively with either GvM or GvHD responses. Conclusions: We successfully established an immunocompetent murine model of graft-versus-myeloma. This is the first immunocompetent murine model which is based on a MM model closely resembling human MM disease (bone marrow tropism, ...) and using allo-SCT after the disease establishment, as a curative treatment [less ▲]

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See detailSex Differences in Abdominal Aortic Aneurysm: the Role of Sex Hormones.
Makrygiannis, Georgios ULg; Courtois, Audrey ULg; Drion, Pierre ULg et al

in Annals of vascular surgery (2014)

Abdominal aortic aneurysm (AAA) is a complex multifactorial disease with genetic and environmental components. AAA is more common in males, whereas women have a greater risk of rupture and more frequently ... [more ▼]

Abdominal aortic aneurysm (AAA) is a complex multifactorial disease with genetic and environmental components. AAA is more common in males, whereas women have a greater risk of rupture and more frequently have concomitant thoracic aortic aneurysms. Moreover, women are diagnosed with AAA about 10 years later and seem to be protected by female sex hormones. In this MEDLINE-based review of literature we examined human and animal, in vivo and in vitro studies, to further deepen our understanding of the sexual dimorphism of AAA. We focus on the role of sex hormones during the formation and growth of AAA. Endogenous estrogens and exogenous 17beta-estradiol were found to exert favorable actions protecting from AAA in animal models, whereas exogenous hormone replacement therapy in humans had inconclusive results. Androgens, known to have detrimental effects in the vasculature, in sufficient levels maintain the integrity of the aortic wall through their anabolic actions and act differentially in males and females, whereas lower levels of testosterone have been associated with AAA in humans. In conclusion, sex differences remain an important area of AAA research, but further studies especially in humans are needed. Furthermore, differential molecular mechanisms of sex hormones constitute a potential therapeutic target for AAA. [less ▲]

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See detailOleuropein or rutin consumption decreases the spontaneous development of osteoarthritis in the Hartley guinea pig.
Horcajada, M.-N.; Sanchez, Christelle ULg; Membrez Scalfo et al

in Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society (2014)

OBJECTIVE: To assess the potential protective effects of three polyphenols oleuropein, rutin and curcumin, on joint ageing and osteoarthritis (OA) development. DESIGN: Sixty 4-week-old Dunkin-Hartley ... [more ▼]

OBJECTIVE: To assess the potential protective effects of three polyphenols oleuropein, rutin and curcumin, on joint ageing and osteoarthritis (OA) development. DESIGN: Sixty 4-week-old Dunkin-Hartley guinea pigs were randomized into four groups and received daily during 31 weeks either standard guinea pig diet (control group) or a standard guinea pig diet enriched with oleuropein (0.025%), rutin (0.5%) or rutin/curcumin (0.5%/0.25%) association. Biomarkers of OA (Coll2-1, Coll2-1NO2, Fib3-1, Fib3-2, ARGS), as well as inflammation (PGE2) were quantified in the serum. Histological assessments of knee cartilage and synovial membrane were performed at week 4 (five young reference guinea pigs) and week 35. RESULTS: At week 35, guinea pigs in the control group spontaneously developed significant cartilage lesions with mild synovial inflammation. The histological scores of cartilage lesions and synovitis were well correlated with the increased level of serum biomarkers. Histologically, all treatments significantly reduced the cartilage degradation score (P < 0.01), but only oleuropein significantly decreased the synovial histological score (P < 0.05) and serum PGE2 levels (P < 0.01) compared to the control group. Coll2-1 was decreased by rutin and the combination of rutin/curcumin, Fib3-1 and Fib3-2 were only decreased by the rutin/curcumin mixture, while Coll2-1NO2 was significantly decreased by all treatments (P < 0.05). CONCLUSION: Oleuropein and rutin +/- curcumin significantly slowed down the progression of spontaneous OA lesions in guinea pigs. While no additive effect was seen in the curcumin + rutin group, the differential effects of oleuropein and rutin on inflammatory and cartilage catabolic markers suggest an interesting combination for future studies in OA protection. [less ▲]

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See detailDUSP3/VHR is a pro-angiogenic atypical dual-specificity phosphatase
Amand, Mathieu ULg; Erpicum, Charlotte ULg; BAJOU, Khalid ULg et al

in Molecular Cancer (2014)

Background DUSP3 phosphatase, also known as Vaccinia-H1 Related (VHR) phosphatase, encoded by DUSP3/Dusp3 gene, is a relatively small member of the dual-specificity protein phosphatases. In vitro studies ... [more ▼]

Background DUSP3 phosphatase, also known as Vaccinia-H1 Related (VHR) phosphatase, encoded by DUSP3/Dusp3 gene, is a relatively small member of the dual-specificity protein phosphatases. In vitro studies showed that DUSP3 is a negative regulator of ERK and JNK pathways in several cell lines. On the other hand, DUSP3 is implicated in human cancer. It has been alternatively described as having tumor suppressive and oncogenic properties. Thus, the available data suggest that DUSP3 plays complex and contradictory roles in tumorigenesis that could be cell type-dependent. Since most of these studies were performed using recombinant proteins or in cell-transfection based assays, the physiological function of DUSP3 has remained elusive. Results Using immunohistochemistry on human cervical sections, we observed a strong expression of DUSP3 in endothelial cells (EC) suggesting a contribution for this phosphatase to EC functions. DUSP3 downregulation, using RNA interference, in human EC reduced significantly in vitro tube formation on Matrigel and spheroid angiogenic sprouting. However, this defect was not associated with an altered phosphorylation of the documented in vitro DUSP3 substrates, ERK1/2, JNK1/2 and EGFR but was associated with an increased PKC phosphorylation. To investigate the physiological function of DUSP3, we generated Dusp3-deficient mice by homologous recombination. The obtained DUSP3-/- mice were healthy, fertile, with no spontaneous phenotype and no vascular defect. However, DUSP3 deficiency prevented neo-vascularization of transplanted b-FGF containing Matrigel and LLC xenograft tumors as evidenced by hemoglobin (Hb) and FITC-dextran quantifications. Furthermore, we found that DUSP3 is required for b-FGF-induced microvessel outgrowth in the aortic ring assay. Conclusions All together, our data identify DUSP3 as a new important player in angiogenesis. [less ▲]

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See detailEstablishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation.
Binsfeld, Marilène ULg; BEGUIN, Yves ULg; Belle, Ludovic et al

in Belgian Journal of Hematology (2014)

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See detailDevice-based controlled local delivery of anastrozol into peritoneal cavity: in vitro and in vivo evaluation
Krier, Fabrice ULg; Riva, Raphaël ULg; Defrère, Sylvie et al

in Journal of Drug Delivery Science and Technology [=JDDST] (2014), 24(2), 198-204

Local treatment using drug loaded implants allows decreasing seric concentrations of the active ingredient with the purpose of limiting side effects and reaching perfect observance. Nowadays, some ... [more ▼]

Local treatment using drug loaded implants allows decreasing seric concentrations of the active ingredient with the purpose of limiting side effects and reaching perfect observance. Nowadays, some diseases are already treated with implants, but generally, by subcutaneous or intra vaginal implantation. In this work, a new implant device dedicated to the intra-peritoneal cavity was developed. For this purpose, a core-membrane polymer implant was selected. We propose an original method to determine the most appropriate membrane to control the release based on the use of Franz cells. The ability of the implant to release a constant quantity of an active ingredient will be assessed by testing implants in vitro. Finally, intra peritoneal cavity and subcutaneous in vivo implantation has been achieved in order to confirm the controlled and local release of the active ingredient. [less ▲]

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See detailEffects of Parecoxib on The Prevention of Postoperative Peritoneal Adhesions in Rats.
Arung, Willy; Jehaes, Francois; Cheramy, Jean-Paul et al

in Journal of Investigative Surgery : The Official Journal of the Academy of Surgical Research (2013), 26(6), 340-346

ABSTRACT Background: No systemic preventive therapy has been successful in inhibiting the development of postoperative peritoneal adhesions (PPAs). Objective: The aim of this study was to evaluate the ... [more ▼]

ABSTRACT Background: No systemic preventive therapy has been successful in inhibiting the development of postoperative peritoneal adhesions (PPAs). Objective: The aim of this study was to evaluate the potential effects of 5 day administration of parecoxib, on PPA prevention and on suture or wound healing in rats. Methods: In a model of PPAs induced by peritoneal electrical burn, 30 rats were randomized into 3 groups according to parecoxib administration route (control; intraperitoneal (IP); intramuscular (IM)). Plasma and peritoneal levels of PAI-1 and tPA were measured at T0, after 90 min of surgery (T90), and on postoperative day 10 (D10). In a cecum resection model, 20 rats were randomized into two groups (control and IP parecoxib), and abdominal wound healing and suture leakage were assessed at D10. In both models, PPAs were evaluated quantitatively and qualitatively on D10. Results: Administration of parecoxib significantly decreased the quantity (p < .05) and the severity (p < .01) of PPAs in both models. In addition, parecoxib administration did not cause healing defects or infectious complications in the two models. In the peritoneal burn model, IP or IM parecoxib administration inhibited the increase of postoperative plasma and peritoneum PAI-1 levels, an increase that was observed in the control group (p < .01). No anastomosis leakage could be demonstrated in both groups in the cecum resection model. Conclusion: This study showed that, in these rat models, parecoxib might reduce PPA formation. Confirmation of the safety of parecoxib on intestinal anastomoses is required and should be investigated in further animal models. [less ▲]

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See detailOleuropein or rutin consumption decreases the spontaneous development of OA in Hartley guinea pig
Sanchez, Christelle ULg; Horcajada, Marie-Noëlle; Membrez, Fanny et al

Conference (2013, November 23)

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See detailLAB’INSIGHT « Toxicological Risk Assessment » - Input of ULg preclinical studies
Drion, Pierre ULg; Remy, Benoît ULg; Winandy, Marie ULg et al

Scientific conference (2013, October 24)

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See detailEffect of Leukocyte- and Platelet-Rich Fibrin (L-PRF) on Bone Regeneration: A Study in Rabbits.
Knapen, Michel; Gheldof, Damien; Drion, Pierre ULg et al

in Clinical Implant Dentistry & Related Research (2013)

BACKGROUND: The positive effect of leukocyte- and platelet-rich fibrin (L-PRF) on osteogenesis has been widely described in vitro. However, clinical and preclinical studies are very little and ... [more ▼]

BACKGROUND: The positive effect of leukocyte- and platelet-rich fibrin (L-PRF) on osteogenesis has been widely described in vitro. However, clinical and preclinical studies are very little and controversial in demonstrating a significant beneficial effect of L-PRF in bone regeneration. PURPOSE: The goal of the present study was to compare the potential effect of L-PRF in a standardized model. MATERIALS AND METHODS: A total of 72 hemispheres were implanted on the calvaria of 18 rabbits and filled with three different space fillers: L-PRF, bovine hydroxyapatite (BHA), BHA + L-PRF, and an empty hemisphere was used as control. Six rabbits were sacrificed at three distinct time points: 1 week, 5 weeks, and 12 weeks. Histological and histomorphometrical analyses were carried out. RESULTS: At the early phase of bone regeneration (1 week), from a descriptive analysis, a higher proportion of connective tissue colonized the regeneration chamber in the two groups containing BHA particles. Nevertheless, no statistical differences were found within the four groups in terms of bone quantity and quality at each timepoint (p = .3623). CONCLUSIONS: According to the present study, L-PRF does not seem to provide any additional effect on the kinetics, quality, and quantity of bone in the present model of guided bone regeneration. [less ▲]

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See detailDevice-based controlled local delivery for the treatment of peritoneal pathologies
Riva, Raphaël ULg; Krier, Fabrice; Defrère, Sylvie et al

Poster (2013, August 18)

This contribution aims at reporting the developpment of a controlled drug delivery system (DDS) dedicated to the treatment of intra-peritoneal pathologies, especially endometriosis. At present time ... [more ▼]

This contribution aims at reporting the developpment of a controlled drug delivery system (DDS) dedicated to the treatment of intra-peritoneal pathologies, especially endometriosis. At present time, endometriosis is generally treated by daily oral absorption of drug with the purpose to improve the life quality of patients by the reduction of the pain caused by endometrial lesions. Nevertheless, deleterious side-effects, mainly infertility, are observed as a consequence of the important amount of absorbed active principle. One main advantage of controlled drug delivery devices, e.g. polymer implants, is to maintain sustained drug release over a prolonged period of time thereby eliminating fluctuations in the drug plasma concentration. Moreover, DDS allows a local release of the drug at a specific area, which significantly decreases the active principle concentration in the body and limits side-effects. The peritoneal cavity is a convenient site for the implantation of a DDS against endometriosis because large parts of lesion are localized in this region. At our knowledge, no application of an implant dedicated to the treatment of endometriosis is reported in the literature, whereas the local controlled release of an active principle presents several advantages compared to systemic administration. In this study, anastrozole (2,2’-[5-1H-1,2,4-triazole-1-yl-methyl)-1,3-phenylene]bis(2-methylpropiononitrile)), a well-known aromatase-inhibiting drug, was selected as active molecule. Typically, two non-biodegradable polymers were tested for the elaboration of an anastrozole loaded intra-peritoneal implant, namely polydimethylsiloxane (PDMS) and poly(ethylene-co-vinyl acetate) (EVA). As preliminary research, the ‘in vivo’ biocompatibility of PDMS and EVA in the intra-peritoneal cavity was confirmed by implantation of PDMS and EVA rod-shaped implants in rats. The kinetic of release was determined ‘in vitro’ and confirmed ‘in vivo’. Besides, the efficiency of the implants was improved by the addition of a polymer membrane, which allowed a controlled release of anastrozole over a period of 400 days. [less ▲]

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