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

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...

Full description

Saved in:

Bibliographic Details
Published in:	Biomaterials Vol. 34; no. 16; pp. 4098 - 4108
Main Authors:	Vilos, Cristian, Morales, Francisco A, Solar, Paula A, Herrera, Natalia S, Gonzalez-Nilo, Fernando D, Aguayo, Daniel A, Mendoza, Hegaly L, Comer, Jeffrey, Bravo, Maria L, Gonzalez, Pamela A, Kato, Sumie, Cuello, Mauricio A, Alonso, Catalina, Bravo, Erasmo J, Bustamante, Eva I, Owen, Gareth I, Velasquez, Luis A
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Ltd 01-05-2013
Subjects:	Advanced Basic Science Cell Death - drug effects Dentistry Drug delivery Endometrial Neoplasms - drug therapy Endometrial Neoplasms - pathology Female G2 Phase Cell Cycle Checkpoints - drug effects Humans M Phase Cell Cycle Checkpoints - drug effects Microscopy, Fluorescence Molecular dynamics simulations Nanoparticle Nanoparticles - toxicity Nanoparticles - ultrastructure Ovarian cancer Ovarian Neoplasms - drug therapy Ovarian Neoplasms - pathology Oxazines - metabolism Paclitaxel Paclitaxel - pharmacology Paclitaxel - therapeutic use Particle Size PHBV Polyesters - toxicity Spectroscopy, Fourier Transform Infrared Static Electricity Time Factors Tumor Cells, Cultured Water - chemistry PHBV Drug delivery Molecular dynamics simulations Nanoparticle Paclitaxel Ovarian cancer
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
ISSN:	0142-9612 1878-5905
DOI:	10.1016/j.biomaterials.2013.02.034