title: Controlling the Release of Proteins from Therapeutic Nanofibers: The Effect of Fabrication Modalities on Biocompatibility and Antimicrobial Activity of Lysozyme.
abstract: Therapeutic application of pharmacologically active proteins requires advanced drug delivery systems for stabilizing their activity and preventing denaturation during storage and patient treatment. Depending on their clinical target, controlled drug release is often required to achieve the intended therapeutic effect. In this context, electrospun nanofibers gained considerable attention. However, even though immediate drug release from such fibers can easily be realized, fiber mat fabrication providing long-term controlled protein release still bares challenges.In this study, lysozyme was encapsulated in poly(vinyl alcohol) fibers followed by post-modification with MeOH, glutaraldehyde vapor, or UV light. Subsequently, a systematic investigation of the effect of these post-modification treatments on the physicochemical properties of the fibers and the stability and release kinetics of lysozyme was performed. MeOH treatment did not affect lysozyme release kinetics compared to untreated fibers, whereas glutaraldehyde vapor and UV light treatment prolonged the drug release. Infrared spectroscopy revealed cross-linking of the polymer by glutaraldehyde vapor, which reduced the lysozyme release from the fibers. Further, protein activity was significantly reduced for fibers treated with glutaraldehyde vapor and UV light. In addition, reduced viability was identified for cells in contact with glutaraldehyde vapor-treated fibers and, to a lesser extent, for UV light-treated fibers, whereas MeOH-treated fibers did not affect cell viability. These results elucidated the effects of fiber post-modification on the release kinetics, activity, and biocompatibility of protein drugs and can serve as guidance for rational development of nanomedicines for safe and effective therapeutic delivery of natural proteins.
authors.affiliation: Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Saarbrücken, Germany.
authors.forename: Salem
authors.initials: S
authors.lastname: Seif
authors.affiliation: Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Saarbrücken, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Planz
authors.affiliation: Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Saarbrücken, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Windbergs
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry; D005976:Glutaral / Q000737:chemistry; D007739:L Cells; D000432:Methanol; D051379:Mice; D009113:Muramidase / Q000008:administration & dosage* / Q000627:therapeutic use; D057139:Nanofibers / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011506:Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D014466:Ultraviolet Rays
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D011506:Proteins; D011142:Polyvinyl Alcohol; D009113:Muramidase; D005976:Glutaral; D000432:Methanol