Lung cancer: a new approach to paclitaxel treatment using PLGA nanocarriers

Julia Jiménez-López

Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.

Julia Jiménez López is a 3º year PhD student at the Institute of Biopathology and Regenerative Medicine (IBIMER) at University of Granada. Her current research is about the improvement of treatment of lung cancer with paclitaxel by encapsulation in polymeric nanoparticles. His work focuses mainly on studying the effectiveness of nanoparticles with paclitaxel compared to free paclitaxel in in vitro and in vivo models.

Maria del Carmen Leiva Arrabal

Maria del Carmen Leiva Arrabal is a 4º year PhD student at the University of Granada, concretelly at the Institute of Biopathology and Regenerative Medicine (IBIMER). Her research is about the delivery of drugs used for the treatment of breast and lung cancer, especially paclitaxel. The aim of her work is to improve the current chemotherapy by incorporating these drugs into nanoparticles to decrease toxicity and enhance their antitumoral effect. She is responsible for the study of the biological activity of the drug-loaded nanoparticles over several tumor models.

Abstract

Introduction
Lung cancer is the type of cancer with the highest mortality rate worldwide. Paclitaxel (PTX), an antimitotic drug, is widely administered for the treatment of choice for this type of cancer and other solid tumours. However, PTX has many limitations and is associated with many undesirable effects like neutropenia, neurotoxicity or hypersensitivity reactions. In this work a new type of polymeric nanoparticles of lactic and glycolic acid (PLGA) loaded with this drug for the treatment of lung cancer is proposed to solve these limitations.

Methods
Proliferation assays with sulforhodamine B in two human lung tumor cell lines, A549 and NCI-H460, were performed in order to compare the effect of free PTX and NPs loaded with this drug (NP-PTX). Cytotoxicity studies with blank nanoparticles were performed. The mechanisms of action of PTX and NP-PTX were tested with cell cycle assays by flow cytometry. For cellular uptake studies with fluorescence microscopy, A549 was incubated with Nile red (NR) and NR-loaded NPs at different times. Finally, multicellular tumour spheroids (MTS) assays in A549 were performed and MTS were treated with PTX, NP-PTX and blank NPs at the IC50 dose of free PTX. MTS growth was monitored with imaging microscopy.

Results
The results obtained in proliferation assays showed significant dose reduction IC50 with NP-PTX up to 3.63 and 3.79 times lower in A549 and NCI-H460, compared to free PTX. No inhibition was observed in the growth of any cell lines with blank nanoparticles. The results showed enhanced cell cycle accumulation in G2 and sub-G1 phase in cells treated with NP-TX facing PTX-treated cells. Intracellular uptake results suggest that NP-PTX facilitate the incorporation of NR into the cell compared with free NR. Finally, the MTS assays showed a significant and greater reduction in the volume of spheroids treated with NP-PTX (73%) than treated with free PTX (46%). No significant difference was observed between MTS untreated and treated with blank NPs.

Discussion
In short, these promising in vitro results obtained suggest that PLGA NPs provide a potential strategy as a mechanism for PTX encapsulation and could allow increasing the therapeutic index of this drug.

Authors

Julia Jiménez-López (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.)
Maria del Carmen Leiva Arrabal (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.)
Mazen El-hammadi (Pharmacy and Pharmaceutical Technology, University of Sevilla)
Laura Cabeza (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.)
Gloria Perazzoli (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.)
Lucía Martín-Banderas (Pharmacy and Pharmaceutical Technology, University of Sevilla)
Raúl Ortiz (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Department of Health Sciences, University of Jaén, Jaén, Spain.)
Jose Prados (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.)
Consolación Melguizo (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.)

Topic Areas

Targeted drug delivery and Nanocarriers , Nanomedecine for cancer diagnosis & therapy

Session

PS2 » Poster Session & Sponsors Exhibition (13:30 - Thursday, 29th September, Patio 25)

Presentation Files

The presenter has not uploaded any presentation files.

Email Support • Blog • Privacy Policy • Cancellation Policy