Paclitaxel-PHBV nanoparticles and their toxicity to endometrial and primary ovarian cancer cells

Cristian Vilos, Francisco A. Morales, Paula A. Solar, Natalia S. Herrera, Fernando D. Gonzalez-Nilo, Daniel A. Aguayo, Hegaly L. Mendoza, Jeffrey Comer, Maria L. Bravo, Pamela A. Gonzalez, Sumie Kato, Mauricio A. Cuello, Catalina Alonso, Erasmo J. Bravo, Eva I. Bustamante, Gareth I. Owen, Luis A. Velasquez

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

This report is an integrated study to include the molecular simulation, physicochemical characterization and biological analysis of a paclitaxel-loaded PHBV nanoparticle that demonstrates uptake, release and cytotoxicity in cancer cell lines. Taking this nanoparticle one step closer to its use in a clinical setting, we demonstrate that it causes significant cell death in primary cultures of stage IIIc serous ovarian cancer cells isolated from six patients. Molecular simulations revealed a high affinity of paclitaxel for the water-polymer interface, thus the drug is delivered only when the polymer near it is degraded. The Fourier transform infrared spectroscopy suggests the formation of a short-lived crystalline phase, also observed in the CG simulations, and transmission electron microscopy revealed branched structures on the surface of particles, which disappeared after 4 days. Biological analyses indicated that these particles have a 48-h window of toxicity protection, allowing for the endocytosis of the particle by the cells; this finding was corroborated by confocal microscopy and flow cytometry. The low cost to synthesize PHBV using microorganisms and the potential chemical modifications of the polymer make it attractive for inexpensive, large-scale pharmaceutical production.

Original languageEnglish
Pages (from-to)4098-4108
Number of pages11
JournalBiomaterials
Volume34
Issue number16
DOIs
Publication statusPublished - May 2013

Keywords

  • Drug delivery
  • Molecular dynamics simulations
  • Nanoparticle
  • Ovarian cancer
  • PHBV
  • Paclitaxel

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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