title: Development of lattice-inserted 5-Fluorouracil-hydroxyapatite nanoparticles as a chemotherapeutic delivery system.
abstract: Developing an effective vehicle for cancer treatment, hydroxyapatite nanoparticles were fabricated for drug delivery. When 5-Fluorouracil, a major chemoagent, is combined with hydroxyapatite nanocarriers by interclay insertion, the modified hydroxyapatite nanoparticles have superior lysosomal degradation profiles, which could be leveraged as controlled drug release. The decomposition of the hydroxyapatite nanocarriers facilitates the release of 5-Fluorouracil into the cytoplasm causing cell death. Hydroxyapatite nanoparticles with/without 5-Fluorouracil were synthesized and analyzed in this study. Their crystallization properties and chemical composition were examined by X-ray diffraction and Fourier transforms infrared spectroscopy. The 5-Fluorouracil release rate was determined by UV spectroscopy. The biocompatibility of hydroxyapatite-5-Fluorouracil extraction solution was assessed using 3T3 cells via a WST-8 assay. The effect of hydroxyapatite-5-Fluorouracil particles which directly work on the human lung adenocarcinoma (A549) cells was evaluated by a lactate dehydrogenase assay via contact cultivation. A 5-Fluorouracil-absorbed hydroxyapatite particles were also tested. Overall, hydroxyapatite-5-Fluorouracils were prepared using a co-precipitation method wherein 5-Fluorouracil was intercalated in the hydroxyapatite lattice as determined by X-ray diffraction. Energy dispersive scanning examination showed the 5-Fluorouracil content was higher in hydroxyapatite-5-Fluorouracil than in a prepared absorption formulation. With 5-Fluorouracil insertion in the lattice, the widths of the a and c axial constants of the hydroxyapatite crystal increased. The extraction solution of hydroxyapatite-5-Fluorouracil was nontoxic to 3T3 cells, in which 5-Fluorouracil was not released in a neutral phosphate buffer solution. In contrast, at a lower pH value (2.5), 5-Fluorouracil was released by the acidic decomposition of hydroxyapatite. Finally, the results of the lactate dehydrogenase assay revealed that 5-Fluorouracil-hydroxyapatite was highly toxic to A549 cells through direct culture, this phenomenon may result from lysosomal decomposition of particles causing 5-Fluorouracil releasing. The pH-responsive hydroxyapatite-5-Fluorouracil nanoparticles have the potential to be part of a selective drug-delivery system in chemotherapy for cancer treatment.
authors.affiliation: Graduate Institute of Biomedical Materials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei City, Taiwan.
authors.forename: Ching-Li
authors.initials: CL
authors.lastname: Tseng
authors.affiliation: Institute of Biomedical Engineering, National Chiao Tung University, Hsinchu City, Taiwan.
authors.forename: Jung-Chih
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Institute of Materials Science and Engineering, National Taipei University of Technology, Taipei City, Taiwan.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei City, Taiwan Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Hsu-Wei
authors.initials: HW
authors.lastname: Fang
authors.affiliation: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli County, Taiwan Institute of Biomedical Engineering, National Taiwan University, Taipei City, Taiwan.
authors.forename: Feng-Huei
authors.initials: FH
authors.lastname: Lin
authors.affiliation: Institute of Materials Science and Engineering, National Taipei University of Technology, Taipei City, Taiwan tptang@ntut.edu.tw.
authors.forename: Tzu-Piao
authors.initials: TP
authors.lastname: Tang
mesh_terms: D016475:3T3 Cells; D000230:Adenocarcinoma / Q000188:drug therapy; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D017886:Durapatite; D005472:Fluorouracil
keywords: 5-Fluorouracil; Hydroxyapatite; cancer; drug delivery system; lattice insertion