Methotrexate-added acrylic cement: biological and physical properties

Maccauro, Giulio; Cittadini, Achille; Casarci, M.; Muratori, Francesco; Angelis, Doina De; Piconi, C.; Rosa, Michele Attilio; Spadoni, A.; Braden, M.; Sgambato, Alessandro

doi:10.1007/s10856-006-0036-7

Cited by 32 publications

(35 citation statements)

References 5 publications

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“…Using MTX-cement as presented above, subsequent drug release did not affect the compressive properties of the cement, and bioactivity was shown up to 30 days [208]. Similar findings were demonstrated by loading custom-made PMMA cement with MTX (4.5 % w/w) since the authors did not detect any changes in the compression modulus of the cement before or after drug elution [209].…”

Section: Drug-releasing Intraosseous Implantssupporting

confidence: 61%

In situ forming implants for local chemotherapy and hyperthermia of bone tumors

Mohamed

Borchard

Jordan

2012

Journal of Drug Delivery Science and Technology

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Hyperthermia, an established adjuvant in cancer treatment, potentiates the effects of anticancer drugs and synergetic combination can be obtained improving the therapeutic outcome. Bone metastases may benefit from this combination when treated through in situ forming implants. Once loaded with magnetizable (nano-) particles and antineoplastic agents, these implants allow for the local application of magnetically-induced hyperthermia and the release of an anticancer drug. The implant can be heated applying an external magnetic field, sensitizing the surrounding tumoral tissues, while releasing the chemotherapeutic agent.Moreover, bone implants provide mechanical support to the weakened bone and consequently relieve pain.This review gives an overview of the current knowledge as well as the rationale of combining locally both magnetic hyperthermia and chemotherapy using in situ forming implants in the field of bone metastases treatment. KeywordsInduced hyperthermia, chemotherapy, drug delivery systems, in situ forming implants, iron oxide nanoparticles, bone metastases, cementoplasty, vertebroplasty 3

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Section: Drug-releasing Intraosseous Implantssupporting

confidence: 61%

In situ forming implants for local chemotherapy and hyperthermia of bone tumors

Mohamed

Borchard

Jordan

2012

Journal of Drug Delivery Science and Technology

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“…[15] Several studies reported the addition of methotrexate to bone fillers, usually PMMA bone cement. [16,17] However, PMMA could only create a burst release. Furthermore the temperatures involved in the polymerization exceeded 60 °C, which was harmful for the surrounding tissues potentially, in poor healers such as treated cancer patients, in particular.…”

Section: Discussionmentioning

confidence: 99%

Collagen membrane wrapping around methotrexate-containing calcium-phosphate cement reduces the side effects on soft tissue healing

Uzun¹,

Akman

Demirkan

et al. 2014

Eklem Hastalik Cerrahisi

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Amaç: Bu çalışmada metotreksat (MTX) içeren kalsiyumfosfat çimentosu (KFÇ) etrafına kollajen membran (membran) sarımının yumuşak doku iyileşmesindeki yan etkileri azaltıp azaltmadığı değerlendirildi. Gereç ve yöntemler: Otuz altı sıçan femurunda kemik defekti oluşturuldu ve sadece KFÇ, etrafı membranla sarılmış KFÇ, %2 MTX içeren KFÇ, etrafı membranla sarılmış ve %2 MTX içeren KFÇ, %5 MTX içeren KFÇ, etrafı membranla sarılmış ve %5 MTX içeren KFÇ şeklinde altı grupta tedavi uygulandı. Bulgular: Histolojik incelemelerde bağ dokusunda etrafı membranla sarılmış %5 MTX içeren grupta, membran içer-meyen %5 MTX'li gruba göre istatistiksel anlamlı şekilde daha iyi bağ doku iyileşmesi görüldü (p= 0.04). Diğer gruplarda buna rastlanmadı. Sonuç: Metotreksat içeren KFÇ'nin etrafının membran ile sarıl-masının, MTX'in hücresel çoğalma üzerinde, özellikle yüksek konsantrasyonlardaki yan etkilerini azaltır. Membran sarımı, antineoplastik ajanların daha yüksek konsantrasyonlarda verilmesini sağlayarak, daha etkili tedavi verilmesini sağlayabilecektir.Anahtar sözcükler: Hayvan modeli; kalsiyum-fosfat çimento; kollajen membran; metotreksat; yumuşak doku iyileşmesi.Objectives: This study aims to evaluate whether the collagen membrane (membrane) wrapping around the methotrexate (MTX)-containing calcium-phosphate cement (CPC) reduces the side effects on soft tissue healing. Material and methods: In 36 rats, femoral bone defects were created and treated in six groups which were CPC only, CPC and membrane wrapping around, CPC containing 2% MTX, CPC containing 2% MTX and membrane wrapping around, CPC containing 5% MTX, CPC containing 5% MTX and membrane wrapping around. Results: Histological examinations revealed a statistically significantly improved healing in the connective tissue samples of the CPC containing 5% MTX group wrapped around by membrane compared to those without membrane (p= 0.04). However, this was not seen in other groups. Conclusion: Membrane wrapping around the CPC containing MTX reduces the side effect of MTX on cellular proliferation at its highest concentration, particularly. Membrane wrapping may allow administration of higher doses of an anti-neoplastic drug which can be more effective.

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“…Hernigou et al [1] reported for the first time that cement implants containing MTX were able to release the drug for a period of months. Subsequent detailed in vitro works evaluated elution kinetics of MTX from the cement pellets [2,4,5]. All authors reported the greatest elution during the first day for all concentrations, with rapid decrease during the following days, and stabilisation to a constant rate of release after two weeks of incubation.…”

Section: Discussionmentioning

confidence: 99%

“…These results accord with the conclusion of Downes [16] who postulated that optimum release is achieved if a crystalline formulation of the drug is used rather than a fine powder. Moreover, Maccauro et al [2] suggested that at the beginning the drug present on the surface of the cement is likely to be eluted. In support of this is the fact that, intensive initial washing of the pellets in saline and ethanol greatly reduced the amount of released MTX from pellets prepared with the liquid form.…”

Section: Discussionmentioning

confidence: 99%

“…Methotrexate (MTX)-loaded bone cement has been suggested as a promising alternative for local chemotherapy of primary and secondary malignant bone tumors after their surgical excision [1,2]. The combination retains useful mechanical properties of polymethylmethacrylate alone and offers the advantage of local cytostatic influence of MTX on remaining tumour cells in surrounding tissue [3,4], as has been shown during a series of in vitro toxicity testing on various cell lines including those from osteosarcoma [1,3,[5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Methotrexate released in vitro from bone cement inhibits human stem cell proliferation in S/G2 phase

Procházka

Soukup

Hroch

et al. 2009

International Orthopaedics (SICOT)

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Methotrexate (MTX) released from bone cement showed a useful local effect in animal models of bone tumours. However, local toxic reactions such as impaired wound healing were observed in areas surrounding the MTX-loaded implant. Therefore, we hypothesised that MTX released from bone cement would have harmful effects on human mesenchymal stem cells (MSC)-one of the basic components of bone marrow and tissue reparatory processes. Moreover, elution of MTX was calculated from implants prepared either with liquid or powdered MTX. During the 28-day incubation, the cement compounded with liquid MTX showed the highest elution rate of the drug. MTX released from pellets produced a significant decrease in proliferation of MSC as a consequence of a blockade of their cell cycle in the S/G2 phase. These findings indicate impairment of stem cell function in marginal areas surrounding the MTX-loaded cement and may help to explain problems with regeneration of tissues in these locations.Résumé Le Methotrexate (MTX) libéré par le ciment acrylique a un effet certain sur les tumeurs osseuses développées sur un modèle animal. Cependant, des réac-tions toxiques locales telles que défauts de cicatrisation ont été observées à proximité de l'implantation de ce ciment. Nous faisons donc l'hypothèse que le Methotrexate MTX libéré par le ciment a un effet nocif néfaste sur les cellules mésenchyméteuses humaines MSC qui sont l'un des composants de base de la moelle osseuse et des phénom-ènes de la réparation tissulaire. De plus, la dynamique de pénétration du méthotrexate a été analysée à partir d'implants préparés avec du liquide ou de la poudre de méthotrexate. Au cours des 28 jours d'incubation, le ciment préparé avec du méthotrexate liquide montre un taux important de pénétration de la drogue. Le méthotrexate libéré des billes de ciment entraîne une diminution significative de la prolifération des cellules mésenchymé-teuses avec un bloquage cellulaire à la phase S/G2. Ces travaux montrent que la fonction cellulaire est altérée au voisInage du méthotrexate pouvant expliquer les problèmes de régénétration tissulaire.

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Methotrexate-added acrylic cement: biological and physical properties

Abstract: These findings confirm the suitability of MTX-supplemented cement and support its use as an effective aid for the management of bone metastases requiring surgical curettage and acrylic cement implantation for structural support.

Cited by 32 publications

References 5 publications

In situ forming implants for local chemotherapy and hyperthermia of bone tumors

In situ forming implants for local chemotherapy and hyperthermia of bone tumors

Collagen membrane wrapping around methotrexate-containing calcium-phosphate cement reduces the side effects on soft tissue healing

Methotrexate released in vitro from bone cement inhibits human stem cell proliferation in S/G2 phase

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