title: Hydroxyapatite nanocrystals as a smart, pH sensitive, delivery system for kiteplatin.
abstract: Hydroxyapatite (HA) nanocrystals are important inorganic constituents of biological hard tissues in vertebrates and have been proposed as a bone substitute or a coating material for prostheses in biomedicine. Hydroxyapatite is also amenable for its capacity to bind to a great variety of biomolecules and therapeutic agents. As drug carriers, apatite nanoparticles also have the advantage of pH dependent solubility and low toxicity. Thus HA nanoparticles are negligibly soluble at physiological pH but their dissolution is accelerated at lower pH such as that typically found in the vicinity of tumors. In the present study we have investigated the adsorption on and the release from biomimetic HA nanoparticles of two platinum derivatives of cis-1,4-diaminocyclohexane ([PtX2(cis-1,4-DACH)], X2 = Cl2 (1) and 1,1-cyclobutanedicarboxylate (CBDCA, 2)). The first of the two compounds proved to be active against colon cancer cells also resistant to oxaliplatin. The release has been investigated as a function of pH to mimic the different physiological environments of healthy tissues and tumors, and the in vitro cytotoxicity of the releasates from the HA matrices has been assessed against various human cancer cell lines. The results fully confirmed the potential of 1-loaded HA nanoparticles as bone-specific drug delivery devices.
authors.affiliation: Bioecoactive S.r.l, via San Donato n.5, 40050 Granarolo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lelli
authors.affiliation: Bioecoactive S.r.l, via San Donato n.5, 40050 Granarolo, Italy.
authors.forename: Norberto
authors.initials: N
authors.lastname: Roveri
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Padova, Via Marzolo 5, 35131, Padova, Italy. valentina.gandina@unipd.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Marzano
authors.affiliation: Department of Chemistry, Eastern Michigan University, 48197 Ypsilanti, MI, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Hoeschele
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy. nicola.margiotta@uniba.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Curci
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy. nicola.margiotta@uniba.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Margiotta
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Padova, Via Marzolo 5, 35131, Padova, Italy. valentina.gandina@unipd.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gandin
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy. nicola.margiotta@uniba.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Natile
mesh_terms: D000327:Adsorption; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D017886:Durapatite / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D009944:Organoplatinum Compounds; C445102:platinum(II)(1,4-diazacycloheptane)dichloride; D017886:Durapatite