Bisphosphonate complexation and calcium doping in silica xerogels as a combined strategy for local and controlled release of active platinum antitumor compounds.

The production of bone substitute biomimetic materials which could also act as antitumoral drug release agents is of enormous interest. We report in this paper the synthesis and characterization of a novel platinum dinuclear complex containing a geminal bisphosphonate and its embodiment into xerogels prepared by the sol-gel method. Our goal was to obtain a hybrid inorganic matrix that could release a platinum species active against bone tumors or metastases, upon local implant. Two silica xerogels were considered: one was composed of pure silica, while the other contained also some calcium as potential release-modulating agent thanks to its high affinity for bisphophonates. The platinum-complex loading capacity of the inorganic matrices, the release kinetics in buffer simulating physiological conditions, and the stability upon storage were investigated as a function of Pt-complex concentration and calcium addition. We found that the presence of calcium in the composites deeply influences not only the stability of the formulations but also the nature of the platinum complex liberated in solution.

Wet sol-gel derived silica for controlled release of proteins.

The potential of wet sol-gel derived silica gels as new matrices for the entrapment and sustained release of proteins was investigated. Model proteins, BSA, ribonuclease-A and avidin, with differing molecular weights and/or isoelectric points, were entrapped in two silica polymer formulations having different silica contents (4% and 12% wt/v). The conformational stability of the proteins after entrapment and their release after immersion into physiological conditions were measured. Circular dichroism analysis showed that protein conformation is maintained after entrapment and stability is enhanced. Protein-free formulations were injected intramuscularly into BALB/c mice to monitor the in vivo fate of the matrix, and the results showed that the gel is totally reabsorbed, without any apparent surrounding inflammation process. The time required for matrix bioerosion varied between one to three weeks, depending on its SiO(2) content. Erosion was also measured in vitro and the contribution of erosion and diffusion to the release of the embedded proteins was quantified. These data indicate that wet silica polymers obtained by the sol-gel route are promising matrices for the sustained release of protein drugs.