Investigation of Molecular Weight, Polymer Concentration and Process Parameters Factors on the Sustained Release of the Anti-Multiple-Sclerosis Agent Teriflunomide from Poly(ε-caprolactone) Electrospun Nanofibrous Matrices

Nikolaos D Bikiaris; Ioanna Koumentakou; Georgia Michailidou; Margaritis Kostoglou; Marilena Vlachou; Panagiotis Barmpalexis; Evangelos Karavas; George Z Papageorgiou

doi:10.3390/pharmaceutics14081693

Investigation of Molecular Weight, Polymer Concentration and Process Parameters Factors on the Sustained Release of the Anti-Multiple-Sclerosis Agent Teriflunomide from Poly(ε-caprolactone) Electrospun Nanofibrous Matrices

Pharmaceutics. 2022 Aug 14;14(8):1693. doi: 10.3390/pharmaceutics14081693.

Authors

Nikolaos D Bikiaris¹, Ioanna Koumentakou¹, Georgia Michailidou¹, Margaritis Kostoglou², Marilena Vlachou³, Panagiotis Barmpalexis⁴, Evangelos Karavas⁵, George Z Papageorgiou⁶

Affiliations

¹ Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
² Laboratory of General and Inorganic Chemical Technology, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
³ Section of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 15784 Athens, Greece.
⁴ Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
⁵ Pharmathen S.A., Pharmaceutical Industry, Dervenakion Str. 6, Pallini Attikis, 15351 Athens, Greece.
⁶ Department of Chemistry, University of Ioannina, P.O. Box 1186, 45110 Ioannina, Greece.

Abstract

In the current work, a series of PCL polyesters with different molecular weights was synthesized and used for the fabrication of nanofibrous patches via electrospinning, as sustained release matrices for leflunomide's active metabolite, teriflunomide (TFL). The electrospinning conditions for each sample were optimized and it was found that only one material with high Mn (71,000) was able to produce structures with distinct fibers devoid of the presence of beads. The successful preparation of the fibers was determined by scanning electron microscopy (SEM).TFL (10, 20 and 30 wt%) in three different concentrations was incorporated into the prepared nanofibers, which were used in in vitro drug release experiments. The drug-loaded nanofibrous formulations were further characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffractometry (XRD).It was found that TFL was incorporated in an amorphous form inside the polymeric nanofibers and that significant molecular interactions were formed between the drug and the polyester. Additionally, in vitro dissolution studies showed that the PCL/TFL-loaded nanofibers exhibit a biphasic release profile, having an initial burst release phase, followed by a sustained release until 250 h. Finally, a kinetic analysis of the obtained profiles revealed that the drug release was directly dependent on the amount TFL incorporated into the nanofibers.

Keywords: drug release; electrospinning; nanofibers; poly(ε-caprolactone) PCL; process parameters; teriflunomide.

Grants and funding

This research received no external funding.