Effect of Paclitaxel/etoposide co-loaded polymeric nanoparticles on tumor size and survival rate in a rat model of glioblastoma

Hassan Maleki; Mohammad Reza Hosseini Najafabadi; Thomas J Webster; Mahmoud Reza Hadjighassem; Esmaeil Sadroddiny; Hossein Ghanbari; Masood Khosravani; Mahdi Adabi

doi:10.1016/j.ijpharm.2021.120722

Effect of Paclitaxel/etoposide co-loaded polymeric nanoparticles on tumor size and survival rate in a rat model of glioblastoma

Int J Pharm. 2021 Jul 15:604:120722. doi: 10.1016/j.ijpharm.2021.120722. Epub 2021 May 20.

Authors

Hassan Maleki¹, Mohammad Reza Hosseini Najafabadi², Thomas J Webster³, Mahmoud Reza Hadjighassem⁴, Esmaeil Sadroddiny⁵, Hossein Ghanbari², Masood Khosravani⁶, Mahdi Adabi⁷

Affiliations

¹ Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
² Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
³ Chemical Engineering Department, Northeastern University, Boston, MA 02115, USA.
⁴ Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: [email protected].
⁷ Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: [email protected].

PMID: 34022255
DOI: 10.1016/j.ijpharm.2021.120722

Abstract

The aim of this work is to co-load paclitaxel (PTX) and etoposide (ETP) in methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (mPEG-PLGA NPs) to overcome pharmacokinetics and physiological limitations and enhance therapeutic efficacy for treating intracranial glioblastoma. Both drugs were loaded into mPEG-PLGA NPs by a nano-precipitation method. The resultant NPs demonstrated an enhanced cytotoxic effect indicated by lower IC₅₀ values and augmented cell apoptosis to U87 and C6 glioma cell lines compared to both free drugs. Additionally, blood compatibility assays showed that the PTX/ETP co-loaded mPEG-PLGA NPs did not induce blood hemolysis, blood clotting, or platelet aggregation. In vivo anti-glioma efficacy evaluation in rats bearingintracranialC6glioma revealed a superior anti-glioma activity for the treatment with PTX/ETP co-loaded mPEG-PLGA NPs compared to other formulations, particularly a significantly longer median survival, 76 days compared to 36 days for free PTX and 37 days for free ETP treatment, respectively, and higher tumor regression, proved by magnetic resonance imaging (MRI).

Keywords: Chemotherapy; Etoposide; Glioblastoma; Nanoparticle; Paclitaxel; mPEG-PLGA.

MeSH terms

Animals
Cell Line, Tumor
Drug Carriers / therapeutic use
Etoposide
Glioblastoma* / drug therapy
Nanoparticles*
Paclitaxel / therapeutic use
Polyethylene Glycols / therapeutic use
Rats
Survival Rate

Substances

Drug Carriers
Polyethylene Glycols
Etoposide
Paclitaxel