title: An injectable calcium phosphate cement for the local delivery of paclitaxel to bone.
abstract: Bone metastases are usually treated by surgical removal, fixation and chemotherapeutic treatment. Bone cement is used to fill the resection voids. The aim of this study was to develop a local drug delivery system using a calcium phosphate cement (CPC) as carrier for chemotherapeutic agents. CPC consisted of alpha-tricalcium phosphate, calcium phosphate dibasic and precipitated hydroxyapatite powders and a 2% Na(2)HPO(4) hardening solution. Scanning electron microscopy (SEM) was used to observe CPC morphology. X-ray diffraction (XRD) was used to follow CPC transformation. The loading/release capacity of the CPC was studied by a bovine serum albumin-loading model. Release/retention was measured by high performance liquid chromatography and X-ray photoelectron spectrometry. For chemotherapeutic loading, paclitaxel (PX) was loaded onto the CPC discs by absorption. Viability of osteosarcoma U2OS and metastatic breast cancer MDA-MB-231 cells was measured by an AlamarBlue assay. Results of SEM and XRD showed changes in CPC due to its transformation. The loading model indicated a high retention behavior by the CPC composition. Cell viability tests indicated a PX minimal lethal dose of 90 μg/ml. PX released from CPC remained active to influence cell viability. In conclusion, this study demonstrated that CPC is a feasible delivery vector for chemotherapeutic agents.
authors.affiliation: Department of Biomaterials, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Lopez-Heredia
authors.forename: G J Bernard
authors.initials: GJ
authors.lastname: Kamphuis
authors.forename: Peter C
authors.initials: PC
authors.lastname: Thüne
authors.forename: F Cumhur
authors.initials: FC
authors.lastname: Öner
authors.forename: John A
authors.initials: JA
authors.lastname: Jansen
authors.forename: X Frank
authors.initials: XF
authors.lastname: Walboomers
mesh_terms: D001682:Biological Availability; D001843:Bone Cements / Q000138:chemical synthesis / Q000737:chemistry*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D001943:Breast Neoplasms / Q000473:pathology; D002130:Calcium Phosphates / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D017886:Durapatite / Q000737:chemistry; D005260:Female; D006801:Humans; D008855:Microscopy, Electron, Scanning; D012516:Osteosarcoma / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D056951:Photoelectron Spectroscopy; D016062:Porosity; D012709:Serum Albumin / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D001843:Bone Cements; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D012709:Serum Albumin; C485828:alpha-tricalcium phosphate; D017886:Durapatite; C485829:calcium phosphate, dibasic, anhydrous; D017239:Paclitaxel