Controlled delivery of bPEI–niclosamide complexes by PEO nanofibers and evaluation of its anti-neoplastic potentials

Abstract

Since the turn of the 21st century, nanofiber based drug delivery systems have evolved drastically to attain controlled and sustained delivery of various bioactive molecules. In spite of such efforts, the tangible interface existing between the target cells and the drug molecules could not be narrowed down. This drawback has been overcome in this work by realizing nanofiber based scaffold for delivery of polymer–drug complexes rather than just the drug. In course with this, in the present study a differentially cross-linkable bPEI-PEO (branched-polyethylenimine-poly(ethylene oxide)) based nanofiber is fabricated for tunable delivery of bPEI–niclosamide complexes. Hydrophilic bPEI–niclosamide complexes are pre-synthesized and stabilized by crosslinking agent, which were then incorporated into bPEI-PEO nanofibers by electrospinning. The niclosamide loaded nanofibers by virtue of bPEI moieties presence were then cross-linked to different degrees which in turn altered bPEI–niclosamide release profile. The release kinetics of bPEI–niclosamide complexes from nanofibers was elucidated further by Korsmeyer-Peppas model. Apart from this, the versatile nature of bPEI-PEO nanofibers was also validated for different drug loading concentration and extent of crosslinking. The fibers antitumor efficacy was then assessed against A549 (Non-small cell lung cancer cells) and U-87 MG (glioblastoma cells) at two different time points (at 48h and 96h) in order to realize the importance of release profile in manifestation of different therapeutic outcomes. Thus, this work endows niclosamide a new life for anticancer application which has remained elusive till date due to its hydrophobic nature.