Next Article in Journal
The Clinical Trial Landscape for Melanoma Therapies
Previous Article in Journal
Fimasartan for Remodeling after Myocardial Infarction
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle

Synergistic Action of Gefitinib and GSK41364A Simultaneously Loaded in Ratiometrically-Engineered Polymeric Nanoparticles for Glioblastoma Multiforme

1
Department of Biomedical Engineering and Biotechnology, University of Massachusetts Lowell, Lowell, MA 01854, USA
2
Department of Chemical Engineering, University of Massachusetts Lowell, Lowell, MA 01854, USA
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(3), 367; https://doi.org/10.3390/jcm8030367
Received: 22 February 2019 / Revised: 8 March 2019 / Accepted: 10 March 2019 / Published: 15 March 2019
(This article belongs to the Section Oncology)
  |  
PDF [4892 KB, uploaded 15 March 2019]
  |     |  

Abstract

Glioblastoma Multiforme is a deadly cancer of glial cells with very low survival rates. Current treatment options are invasive and have serious side effects. Single drug treatments make the tumor refractory after a certain period. Combination therapies have shown improvements in treatment responses against aggressive forms of cancer and are becoming a mainstay in the management of cancer. The purpose of this study is to design a combinatorial treatment regimen by engineering desired ratios of two different small molecule drugs (gefitinib and GSK461364A) in a single carrier that can reduce off-target effects and increase their bioavailability. Synergistic effects were observed with our formulation when optimal ratios of gefitinib and GSK461364A were loaded in poly (lactic-co-glycolic) acid and polyethylene glycol (PLGA-PEG) nanoparticles and tested for efficacy in U87-malignant glioma (U87-MG) cells. Combination nanoparticles proved to be more effective compared to single drug encapsulated nanoparticles, free drug combinations, and the mixture of two single loaded nanoparticles, with statistically significant values at certain ratios and drug concentrations. We also observed drastically reduced clonogenic potential of the cells that were treated with free drugs and nanoparticle combinations in a colony forming assay. From our findings, we conclude that the combination of GSK461364A and higher concentrations of gefitinib when encapsulated in nanoparticles yield synergistic killing of glioma cells. This study could form the basis for designing new combination treatments using nanoparticles to deliver multiple drugs to cancer cells for synergistic effects. View Full-Text
Keywords: combination therapy; cancer; glioblastoma multiforme; polymeric nanoparticles; gefitinib; GSK461364A; drug resistance; synergistic effect; drug interaction; enhanced permeation and retention combination therapy; cancer; glioblastoma multiforme; polymeric nanoparticles; gefitinib; GSK461364A; drug resistance; synergistic effect; drug interaction; enhanced permeation and retention
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Velpurisiva, P.; Rai, P. Synergistic Action of Gefitinib and GSK41364A Simultaneously Loaded in Ratiometrically-Engineered Polymeric Nanoparticles for Glioblastoma Multiforme. J. Clin. Med. 2019, 8, 367.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top