Development of Epirubicin-Loaded Biocompatible Polymer PLA-PEG-PLA Nanoparticles: Synthesis, Characterization, Stability, and In Vitro Anticancerous Assessment.

Salam Massadeh,Nouf Aldhawi,Iman Almohammed,Mustafa Omer,Manal Alaamery,Abdulaziz Almalik,Eman Barhoush

doi:10.3390/polym13081212

Abstract

Epirubicin (EPI) is an anti-cancerous chemotherapeutic drug that is an effective epimer of doxorubicin with less cardiotoxicity. Although EPI has fewer side effects than its analog, doxorubicin, this study aims to develop EPI nanoparticles as an improved formula of the conventional treatment of EPI in its free form. Methods: In this study, EPI-loaded polymeric nanoparticles (EPI-NPs) were prepared by the double emulsion method using a biocompatible poly (lactide) poly (ethylene glycol) poly(lactide) (PLA–PEG–PLA) polymer. The physicochemical properties of the EPI-NPs were determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), entrapment efficiency and stability studies. The effect of EPI-NPs on cancer cells was determined by high throughput imaging and flow cytometry. Results: The synthesis process resulted in monodisperse EPI-NPs with a size of 166.93 ± 1.40 nm and an elevated encapsulation efficiency (EE) of 88.3%. In addition, TEM images revealed the spherical uniformness of EPI-NPs with no aggregation, while the cellular studies presented the effect of EPI-NPs on MCF-7 cells’ viability; after 96 h of treatment, the MCF-7 cells presented considerable apoptotic activity. The stability study showed that the EPI-NPs remained stable at room temperature at physiological pH for over 30 days. Conclusion: EPI-NPs were successfully encapsulated within a highly stable biocompatible polymer with minimal loss of the drug. The used polymer has low cytotoxicity and EPI-NPs induced apoptosis in estrogen-positive cell line, making them a promising, safe treatment for cancer with less adverse side effects.

Highlights

Epirubicin (EPI) is a chemotherapy anthracycline drug that is less cardiotoxic and more effective than its widely used derivative, doxorubicin [1]; it is recommended as a suitable alternative to doxorubicin [2]
The double emulsion method provides the nanoparticles with the controlled release feature, which makes them suitable candidates as sustained release drug delivery systems [43,44]
The poly lactic acid (PLA)–poly ethylene glycol (PEG)–PLA amphiphilic polymer was dissolved in chloroform, and the EPI was dissolved in dimethyl sulfoxide (DMSO); both solutions were ultra-sonicated to form the first emulsion

Summary

Introduction

Epirubicin (EPI) is a chemotherapy anthracycline drug that is less cardiotoxic and more effective than its widely used derivative, doxorubicin [1]; it is recommended as a suitable alternative to doxorubicin [2]. It has been proven to be effective to treat lung, liver, and breast cancer [3,4,5,6,7]. EPI forms a complex with DNA and eventually inhibits the synthesis of macromolecules [8]. Additional studies reported that EPI acts by the generation of free radicals, which leads to DNA damage or lipid peroxidation. It was suggested that EPI affects the cell membrane by inhibiting topoisomerase II directly, which induces apoptosis [4,9]. The conventional dosage form of EPI is administered as an intravenous solution for cancer therapy. The current treatment is effective, it causes severe side effects such as secondary malignancies, extravasation, and tissue necrosis [4]

Objectives

Methods

Results

Conclusion