Amphiphilic Block Copolymer Microspheres Derived from Castor Oil, Poly(ε-carpolactone), and Poly(ethylene glycol): Preparation, Characterization and Application in Naltrexone Drug Delivery

Maria Nerantzaki; Eirini Skoufa; Kyriakos-Vasileios Adam; Stavroula Nanaki; Apostolos Avgeropoulos; Margaritis Kostoglou; Dimitrios Bikiaris

doi:10.3390/ma11101996

Amphiphilic Block Copolymer Microspheres Derived from Castor Oil, Poly(ε-carpolactone), and Poly(ethylene glycol): Preparation, Characterization and Application in Naltrexone Drug Delivery

Materials (Basel). 2018 Oct 16;11(10):1996. doi: 10.3390/ma11101996.

Authors

Maria Nerantzaki^{1

2}, Eirini Skoufa³, Kyriakos-Vasileios Adam⁴, Stavroula Nanaki⁵, Apostolos Avgeropoulos⁶, Margaritis Kostoglou⁷, Dimitrios Bikiaris⁸

Affiliations

¹ Physicochemistry Laboratory of Electrolytes and Interfacial Nanosystems (PHENIX), UMR CNRS 8234, Faculty of Science and Engineering, Sorbonne University, 75252 Paris CEDEX 05, France. marinera002@msn.com.
² Laboratory of Chemistry and Technology of Polymers and Dyes, Chemistry Department, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. marinera002@msn.com.
³ Laboratory of Polymeric Materials, Department of Materials Science and Engineering, University of Ioannina, Administration Building, University Campus Dourouti, 45110 Ioannina, Greece. eiriniskoufa@gmail.com.
⁴ Laboratory of Chemistry and Technology of Polymers and Dyes, Chemistry Department, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. kva.adam@gmail.com.
⁵ Laboratory of Chemistry and Technology of Polymers and Dyes, Chemistry Department, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. sgnanaki@chem.auth.gr.
⁶ Laboratory of Polymeric Materials, Department of Materials Science and Engineering, University of Ioannina, Administration Building, University Campus Dourouti, 45110 Ioannina, Greece. aavger@cc.uoi.gr.
⁷ Laboratory of General and Inorganic Chemical Technology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. kostoglu@chem.auth.gr.
⁸ Laboratory of Chemistry and Technology of Polymers and Dyes, Chemistry Department, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. dbic@chem.auth.gr.

Abstract

In the present study, the newly synthesized castor oil-derived thioether-containing ω-hydroxyacid (TEHA) block copolymers with polycaprolactone (TEHA-b-PCL), with methoxypoly(ethylene glycol) (mPEG), (TEHA-b-mPEG) and with poly(ethylene glycol) (PEG) (TEHA-b-PEG-b-TEHA), were investigated as polymeric carriers for fabrication of naltrexone (NLX)-loaded microspheres by the single emulsion solvent evaporation technique. These microspheres are appropriate for the long-term treatment of opioid/alcohol dependence. Physical properties of the obtained microspheres were characterized in terms of size, morphology, drug loading capacity, and drug release. A scanning electron microscopy study revealed that the desired NLX-loaded uniform microspheres with a mean particle size of 5⁻10 µm were obtained in all cases. The maximum percentage encapsulation efficiency was found to be about 25.9% for the microspheres obtained from the TEHA-b-PEG-b-TEHA copolymer. Differential scanning calorimetry and X-ray diffractometry analysis confirmed the drug entrapment within microspheres in the amorphous state. In vitro dissolution studies revealed that all NLX-loaded formulations had a similar drug release profile: An initial burst release after 24 h, followed by a sustained and slower drug release for up to 50 days. The analysis of the release kinetic data, which were fitted into the Korsmeyer⁻Peppas release model, indicated that diffusion is the main release mechanism of NLX from TEHA-b-PCL and TEHA-b-mPEG microspheres, while microspheres obtained from TEHA-b-PEG-b-TEHA exhibited a drug release closer to an erosion process.

Keywords: amphiphilic block copolymers; castor oil; drug release; microspheres; naltrexone; poly(ethylene glycol); poly(ε-caprolactone).