A POLYMER-BASED DRUG-DELIVERY SYSTEM FOR THE ANTINEOPLASTIC AGENT BIS(MALTOLATO)OXOVANADIUM IN MICE

Using vanadyl sulphate, sodium orthovanadate or bis(maltolato)oxovanad ium (BMOV), Cruz TF, Morgan A, Min W (1995, Mol Cell Biochem 153: 161- 166) have recently demonstrated the antineoplastic effects of vanadium in mice. In this study, the antineoplastic effects of BMOV against hu man tumour cell lines was confirmed, and this effect was shown to depe nd on the prolonged exposure of the cells to the drug. We have investi gated a polymeric drug delivery system for the sustained delivery of B MOV as an antineoplastic agent in mice. The objective was to design an d evaluate an injectable polymer-BMOV paste that would act as a drug i mplant for the slow but sustained release of BMOV in the mice. In vitr o studies showed that the biodegradable polymer poly (Ghlr epsilon eps ilon-caprolactone) (PCL) released BMOV in a sustained manner with rate s of drug release increasing with increased loading of the drug in the polymer. In vivo studies showed that PCL-BMOV paste implants produced a concentration-dependent inhibition of MDAY-D2 tumour growth via sys temic drug delivery. Further in vivo studies showed that 5% BMOV-loade d PCL (containing 20% methoxypolyethylene glycol) was effective in pre venting tumour regrowth of resected RIF tumour masses in mice when the PCL-BMOV paste was applied to the resected site far localized drug de livery. The results confirm the potential of vanadium as an antineopla stic agent and show that the injectable PCL-BMOV formulation releases a chemotheraputic dose of vanadium for the systemic treatment of whole tumours as well as the localized treatment of resected RIF tumours.