Development of lattice-inserted 5-Fluorouracil-hydroxyapatite nanoparticles as a chemotherapeutic delivery system

Ching Li Tseng, Jung Chih Chen, Yu Chun Wu, Hsu Wei Fang, Feng Huei Lin, Tzu Piao Tang

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)388-397
Number of pages10
JournalJournal of Biomaterials Applications
Volume30
Issue number4
DOIs
Publication statusPublished - Oct 1 2015

Fingerprint

Durapatite
Hydroxyapatite
Fluorouracil
Nanoparticles
Assays
Oncology
Decomposition
L-Lactate Dehydrogenase
X ray diffraction
Chemotherapy
Cell death
Coprecipitation
Poisons
Ultraviolet spectroscopy
Drug delivery
Biocompatibility
Crystallization
Fourier transform infrared spectroscopy

Keywords

  • 5-Fluorouracil
  • cancer
  • drug delivery system
  • Hydroxyapatite
  • lattice insertion

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials

Cite this

Development of lattice-inserted 5-Fluorouracil-hydroxyapatite nanoparticles as a chemotherapeutic delivery system. / Tseng, Ching Li; Chen, Jung Chih; Wu, Yu Chun; Fang, Hsu Wei; Lin, Feng Huei; Tang, Tzu Piao.

In: Journal of Biomaterials Applications, Vol. 30, No. 4, 01.10.2015, p. 388-397.

Research output: Contribution to journalArticle

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