title: Bisphosphonate complexation and calcium doping in silica xerogels as a combined strategy for local and controlled release of active platinum antitumor compounds.
abstract: 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.
authors.affiliation: Dipartimento Farmaco-Chimico, Università degli Studi di Bari. Via E. Orabona 4, 70125 Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Margiotta
authors.forename: Rosa
authors.initials: R
authors.lastname: Ostuni
authors.forename: Deborah
authors.initials: D
authors.lastname: Teoli
authors.forename: Margherita
authors.initials: M
authors.lastname: Morpurgo
authors.forename: Nicola
authors.initials: N
authors.lastname: Realdon
authors.forename: Barbara
authors.initials: B
authors.lastname: Palazzo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Natile
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy*; D018786:Bone Substitutes / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D002118:Calcium / Q000737:chemistry; D003692:Delayed-Action Preparations; D004164:Diphosphonates / Q000737:chemistry; D005782:Gels; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000737:chemistry* / Q000627:therapeutic use; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D018786:Bone Substitutes; D003692:Delayed-Action Preparations; D004164:Diphosphonates; D005782:Gels; D009944:Organoplatinum Compounds; D012822:Silicon Dioxide; D002118:Calcium