Paclitaxel Magnetic Core⁻Shell Nanoparticles Based on Poly(lactic acid) Semitelechelic Novel Block Copolymers for Combined Hyperthermia and Chemotherapy Treatment of Cancer.

Evi Christodoulou,Dimitrios N Bikiaris,Kleoniki Giannousi,Eleni Gounari,Panagiotis Barmpalexis,Antonis D Anastasiou,Catherine Dendrinou-Samara,Makis Angelakeris,Maria Nerantzaki,Stavroula Nanaki

doi:10.3390/pharmaceutics11050213

Evi Christodoulou, Dimitrios N Bikiaris + Show 8 more

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https://doi.org/10.3390/pharmaceutics11050213

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Abstract

Magnetic hybrid inorganic/organic nanocarriers are promising alternatives for targeted cancer treatment. The present study evaluates the preparation of manganese ferrite magnetic nanoparticles (MnFe2O4 MNPs) encapsulated within Paclitaxel (PTX) loaded thioether-containing ω-hydroxyacid-co-poly(d,l-lactic acid) (TEHA-co-PDLLA) polymeric nanoparticles, for the combined hyperthermia and chemotherapy treatment of cancer. Initially, TEHA-co-PDLLA semitelechelic block copolymers were synthesized and characterized by 1H-NMR, FTIR, DSC, and XRD. FTIR analysis showed the formation of an ester bond between the two compounds, while DSC and XRD analysis showed that the prepared copolymers were amorphous. MnFe2O4 MNPs of relatively small crystallite size (12 nm) and moderate saturation magnetization (64 emu·g−1) were solvothermally synthesized in the sole presence of octadecylamine (ODA). PTX was amorphously dispersed within the polymeric matrix using emulsification/solvent evaporation method. Scanning electron microscopy along with energy-dispersive X-ray spectroscopy and transmission electron microscopy showed that the MnFe2O4 nanoparticles were effectively encapsulated within the drug-loaded polymeric nanoparticles. Dynamic light scattering measurements showed that the prepared nanoparticles had an average particle size of less than 160 nm with satisfactory yield and encapsulation efficiency. Diphasic PTX in vitro release over 18 days was observed while PTX dissolution rate was mainly controlled by the TEHA content. Finally, hyperthermia measurements and cytotoxicity studies were performed to evaluate the magnetic response, as well as the anticancer activity and the biocompatibility of the prepared nanocarriers.

Highlights

The smart design and tailoring properties of several nanoparticle based drug delivery systems (DDS) has led to their extensive investigation as an alternative new approach for targeted and more effective treatment of cancer [1,2]
The present study evaluates the preparation of manganese ferrite magnetic nanoparticles (MnFe2O4 MNPs) encapsulated within Paclitaxel (PTX) loaded thioether-containing ω-hydroxyacid-co-poly(d,l-lactic acid) (TEHA-co-PDLLA) polymeric nanoparticles, for the combined hyperthermia and chemotherapy treatment of cancer
MnFe2O4 nanoparticles were encapsulated in PXT loaded polymeric nanoparticles based on TEHA-co-PDLLA semitelechelic block copolymers

Summary

Introduction

The smart design and tailoring properties of several nanoparticle based drug delivery systems (DDS) has led to their extensive investigation as an alternative new approach for targeted and more effective treatment of cancer [1,2]. These nano-based systems may be prepared from either organic (such as biocompatible polymers), or inorganic (such as iron oxides) materials, recent attempts are focused on the development of novel systems combining both [3,4,5]. Hyperthermia induced cancer therapy refers to a small temperature rise (from 41 to 45 ◦C) which leads to cell death through the initiation of a series of pro-apoptotic and apoptotic signaling cascades [20]

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