title: Influence of spray-dried hydroxyapatite-5-fluorouracil granules on cell lines derived from tissues of mesenchymal origin.
abstract: In our previous work we described the preparation and characterization of spray dried hydroxyapatite micro granules loaded with 5-fluorouracil (5-FU). These loaded particles are used as a model drug delivery system (DDS). In this study we examined the in vitro response of two cell lines derived from different tissues to 5-FU loaded granules (LG). Both cell lines, either L929 cells of a mouse fibroblast lineage or cells originating from a rat osteosarcoma (ROS 17/2.8) showed a dose dependent decrease in cell proliferation in response to 5-FU-, either dissolved in the culture medium or loaded onto particles. The response of the two cell lines to loaded and nonloaded particles was different. The effect of LG and of a corresponding concentration of free 5-FU was practically the same for the ROS 17/2.8 cells indicating that ROS 17/2.8 cells were not affected by the carrier material. In contrast, L929 cells showed a slight decrease in cell proliferation also in the presence of granules not loaded with 5-FU. This is thought to be attributed to the inhibition of mitogenesis by phosphocitrates, already demonstrated in fibroblasts. In summary, we found that the loaded 5-FU kept its effectivity after the spray drying process and that the response towards the granules varied with cell type. This is the first step towards a tissue specific DDS.
authors.affiliation: Institute for Biological Interfaces; Forschungszentrum Karlsruhe GmbH, 76344 Eggenstein- Leopoldshafen Karlsruhe, Germany. tim.scharnweber@ibg.fzk.de
authors.forename: Tim
authors.initials: T
authors.lastname: Scharnweber
authors.forename: Catarina
authors.initials: C
authors.lastname: Santos
authors.forename: Ralf-Peter
authors.initials: RP
authors.lastname: Franke
authors.forename: Maria Margarida
authors.initials: MM
authors.lastname: Almeida
authors.forename: Maria Elisabete V
authors.initials: ME
authors.lastname: Costa
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D017886:Durapatite / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005472:Fluorouracil / Q000737:chemistry / Q000494:pharmacology*; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D012516:Osteosarcoma / Q000473:pathology; D051381:Rats
chemical_list: D000964:Antimetabolites, Antineoplastic; D017886:Durapatite; D005472:Fluorouracil