Antimicrobial Activity of Poly(ester urea) Electrospun Fibers Loaded with Bacteriophages

Abstract

The capacity to load bacteriophages into electrospun nanofibers of two representative biocompatible polymers has been evaluated, paying special attention to the possibility of preserving their antibacterial activity. Specifically, the work involves the following steps: (a) Evaluation of the effect of the applied electrical field on the phage activity; (b) evaluation of the activity when a lyophilization process could be avoided by using water soluble polymers (e.g., poly(ethylene glycol); (c) evaluation of the activity when dissolution of the polymer requires an organic solvent and lyophilization is theoretically necessary. In this case, a poly(ester urea) (PEU) derived from the natural L-leucine amino acid has been considered. Adsorption of commercial bacteriophage preparations into calcium carbonate particles was demonstrated to be a promising methodology to avoid lyophilization and keep the initial bactericide activity at a maximum. Phagestaph and Fersis bacteriophage commercial preparations have been selected for this study due to their specific activity against Staphylococci (e.g., S. aureus) and Streptococci (e.g., S. pyogenes) bacteria. Adhesion and proliferation assays using epithelial cells demonstrated the biocompatibility of both unloaded and bacteriophage-loaded PEU scaffolds, although some slight differences were observed depending on the type of bacteriophage and the selected preparation methodology.

Formulations for Bacteriophage Therapy and the Potential Uses of Immobilization

“…Viability during the electrospinning process as well as during subsequent storage may be improved by adding magnesium salts and excipients such as trehalose [ 80 ]. Despite these observations, Diaz et al (2018) demonstrated the applicability of the electrospinning process to a broad range of bacteriophages by integrating Fersis and PhageStaph commercial phage cocktails into nanofibers formed from a soluble (polyethylene glycol) and biodegradable polymer (polyester urea) [ 81 ]. Viable phage titers were broadly conserved across samples, with a slight decrease in the case of polyester urea fibers when lyophilized phage was used instead of the original solutions, and with the resultant nanofibers demonstrating antimicrobial activity against corresponding bacterial hosts, inhibiting growth for up to 80 h after exposure.…”

Bacteriophage and Endolysin Encapsulation Systems: A Promising Strategy to Improve Therapeutic Outcomes

“…Polycaprolactone electrospun nanofibers based phage encapsulation also showed a 99.99% decrement of Pseudomonas aeruginosa population in 2 h (Nogueira et al, 2017). In a recent study, Phagestaph and Fersis phages were encapsulated and evaluated for their biocompatibility and antibacterial activity against S. aureus and Streptococcus pyogenes (Díaz et al, 2018). However, the electrospun phage delivery system's therapeutic applicability is limited to in-vitro experiments requiring more extensive validation, especially in animal infection models.…”

Review of Possible Applications of Nanofibrous Mats for Wound Dressings

“…Frequently used polymers which are spinnable from non-toxic or low-toxic solvents are, for example, polyacrylonitrile (PAN, spinnable from dimethyl sulfoxide, DMSO) and poly(ethylene glycol) (PEG, spinnable from water) [43][44][45]. PEO and PVA are oft en used as the spinning agent for materials which cannot form fi bres solely [46].…”