Extended immunosuppression with cyclophosphamide using controlled-release polymeric implants.

An effective method of prolonged immunosuppressive therapy using cyclophosphamide incorporated into acrylic bone cement has been developed. We have studied the effect of this form of administration of cyclophosphamide on circulating immune cells and the inflammatory response. When the slow release mode of cyclophosphamide administration was compared with conventional systemic therapy, it was found to produce a more rapid and prolonged immunosuppression. A dose-response relationship was established and the biological effects of varying the composition and surface area of the implant were determined. The inflammatory response, assessed by measuring the mobilisation of cells into subcutaneously implanted sponges, was also depressed using this mode of administration. These results, coupled with the commercial availability and existing clinical approval of Simplex P bone cement, suggest that the procedure could lead to useful clinical protocols.