Development of lattice-inserted 5-Fluorouracil-hydroxyapatite nanoparticles as a chemotherapeutic delivery system
Journal
Journal of Biomaterials Applications
Journal Volume
30
Journal Issue
4
Pages
388-397
Date Issued
2015
Author(s)
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. ? SAGE Publications.
SDGs
Other Subjects
Biocompatibility; Cell death; Cells; Chemotherapy; Cytology; Diseases; Drug products; Extraction; Fourier transforms; Infrared spectroscopy; Lattice constants; Nanoparticles; Precipitation (chemical); Synthesis (chemical); Ultraviolet spectroscopy; X ray diffraction; 5-fluorouracil; cancer; Crystallization properties; Drug delivery system; Fourier transforms infrared spectroscopies; Hydroxyapatite nanoparticles; Lactate dehydrogenase assays; lattice insertion; Hydroxyapatite; fluorouracil; hydroxyapatite; lactate dehydrogenase; nanoparticle; phosphate; antineoplastic antimetabolite; drug carrier; fluorouracil; hydroxyapatite; nanoparticle; 3T3 cell line; A549 cell line; acidity; animal cell; antineoplastic activity; Article; biocompatibility; cancer chemotherapy; chemical composition; controlled study; crystal structure; crystallization; culture technique; decomposition; drug absorption; drug cytotoxicity; drug delivery system; drug effect; drug formulation; drug release; enzyme assay; human; human cell; infrared spectroscopy; intercalation complex; lysosome; mouse; nonhuman; precipitation; priority journal; synthesis; ultraviolet spectroscopy; X ray diffraction; adenocarcinoma; animal; chemistry; Lung Neoplasms; tumor cell line; ultrastructure; 3T3 Cells; Adenocarcinoma; Animals; Antimetabolites, Antineoplastic; Cell Line, Tumor; Drug Carriers; Durapatite; Fluorouracil; Humans; Lung Neoplasms; Mice; Nanoparticles
Type
journal article