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

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

doi:10.3390/pharmaceutics11050213

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

Pharmaceutics. 2019 May 3;11(5):213. doi: 10.3390/pharmaceutics11050213.

Affiliations

¹ Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. evicius@gmail.com.
² Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. marinera002@msn.com.
³ Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. sgnanaki@chem.auth.gr.
⁴ Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. pbarmp@pharm.auth.gr.
⁵ Laboratory of Inorganic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. klegia@chem.auth.gr.
⁶ Laboratory of Inorganic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. samkat@chem.auth.gr.
⁷ Department of Physics, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. agelaker@auth.gr.
⁸ Biohellenika Biotechnology Company, Leoforos Georgikis Scholis 65, 57001 Thessaloniki, Greece. eleni-790@hotmail.com.
⁹ School of Chemical and Process Engineering, University of Leeds, Leeds LS2 9JT, UK. A.Anastasiou@leeds.ac.uk.
¹⁰ Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. dbic@chem.auth.gr.

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.

Keywords: Paclitaxel; block copolymers; chemotherapy; drug delivery; hyperthermia; magnetic core–shell nanoparticles; nanocarriers; poly(lactic acid); polyesters.