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DELIVERY OF CHEMOTHERAPY USING POLYMETHYLMETHACRYLATE CEMENT: AN ANIMAL MODEL

U.S.A.

Aim: To investigate the possibility of using polymethylmethacrylate (PMMA) bone cement as a delivery vehicle for anti-tumour chemotherapy.

Methods: Doxorubicin was incorporated into PMMA pellets and incubated in physiological medium at 37°C. Release of Doxorubicin from the pellets continued for eight weeks as demonstrated by high performance liquid chromatography (HPLC).

Doxorubicin-containing pellets were incubated with sarcoma cultures at 37°C for 24 hours. A significantly higher cell death rate(as measured by flow cytometry) was seen in the plates exposed to Doxorubicin compared to those exposed only to plain PMMA, indicating that the Doxorubicin released from the cement pellets retained its cytotoxic capability.

PMMA-Doxorubicin cement pellets were implanted in rat tibiae and the animals killed at intervals over three weeks. HPLC analysis showed that this technique produced high concentrations of Doxorubicin adjacent to the implant but negligible systemic levels(heart, kidney, lung, liver).

Four groups of rats had sarcomas established in their tibiae and then treated either by excision of tumour and Doxorubicin/PMMA implantation, excision and plain PMMA implantation, excision only or no treatment. The animals were then observed for tumour regrowth. A survival advantage was demonstrated for those animals treated by tumour excision and Doxorubicin/PMMA implantation.

Conclusion: These experiments demonstrate that PMMA is an effective medium for the delivery of cytotoxic chemotherapy. This method has scope for early translation to the human situation.

The abstracts were prepared by Mr Ray Moran. Correspondence should be addressed to him at the Irish Orthopaedic Association, Secretariat, c/o Cappagh Orthopaedic Hospital, Finglas, Dublin