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Planta Med 2017; 83(05): 445-452
DOI: 10.1055/s-0042-109715
Formulation and Delivery Systems of Natural Products
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Controlling the Release of Proteins from Therapeutic Nanofibers: The Effect of Fabrication Modalities on Biocompatibility and Antimicrobial Activity of Lysozyme

Salem Seif
1   Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Saarbrücken, Germany
2   PharmBioTec GmbH, Saarbrücken, Germany
,
Viktoria Planz
1   Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Saarbrücken, Germany
3   Helmholtz Centre for Infection Research (HZI) and Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Delivery (DDEL), Saarbrücken, Germany
,
Maike Windbergs
1   Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Saarbrücken, Germany
2   PharmBioTec GmbH, Saarbrücken, Germany
3   Helmholtz Centre for Infection Research (HZI) and Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Delivery (DDEL), Saarbrücken, Germany
› Author Affiliations
Further Information

Publication History

received 01 January 2016
revised 13 April 2016

accepted 24 May 2016

Publication Date:
28 June 2016 (online)

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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.

Key words

lysozyme - electrospinning - nanomedicines - controlled release - protein activity - antimicrobials
 

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