Electrospun Fibers for Controlled Release of Nanoparticle-Assisted Phage Therapy Treatment of Topical Wounds

Abstract

ABSTRACTBacterial cultures exposed to iron-doped apatite nanoparticles (IDANPs) prior to the introduction of antagonistic viruses experience up to 2.3 times the bacterial destruction observed in control cultures. Maximum antibacterial activity of these bacteria-specific viruses, or phage, occurs after bacterial cultures have been exposed to IDANPs for 1 hr prior to phage introduction, demonstrating that IDANP-assisted phage therapy would not be straight forward, but would instead require controlled time release of IDANPs and phage. These findings motivated the design of an electrospun nanofiber mesh treatment delivery system that allows burst release of IDANPs, followed by slow, consistent release of phage for treatment of topical bacterial infections. IDANPs resemble hydroxyapatite, a biocompatible mineral analogous to the inorganic constituent of mammalian bone, which has been approved by the Food and Drug Administration for many biomedical purposes. The composite nanofiber mesh was designed for IDANP-assisted phage therapy treatment of topical wounds and consists of a superficial, rapid release layer of polyethylene oxide (PEO) fibers doped with IDANPs, followed by inner, coaxial polycaprolactone / polyethylene glycol (PCL/PEG) blended polymer fiber layer for slower phage delivery. Our investigations have established that IDANP-doped PEO fibers are effective vehicles for dissemination of IDANPs for bacterial exposure and resultant increased bacterial death by phage. In this work, slower delivery of the phage behind IDANPs was accomplished using coaxial, electrospun fibers composed of PCL/PEG polymer blend.