Hydrogel formulations containing non-ionic polymers for topical delivery of bacteriophages

Hydrogel is an attractive delivery vehicle for phages as it keeps the wound moist, acts as a protective barrier and facilitates wound healing process. The aim of this study was to formulate biologically stable phage hydrogels that enable controlled release of infective phages. Pseudomonas-targeting phages, PEV1 (myovirus) and PEV31 (podovirus) were formulated in hydrogels (10⁹ PFU/g) consisting of non-ionic polymers, including hydroxyethyl cellulose (HEC), hydroxypropyl methylcellulose (HPMC), polyethylene oxide (PEO), polyvinyl alcohol (PVA), hydroxypropyl cellulose (HPC) and polyvinylpyrrolidone (PVP). The formulations were evaluated for physical properties, in vitro release profiles, antibacterial activity, and storage stability. Controlled release of phages was observed in 7.5% PEO, 20% PVA and 75% PVP hydrogels with >10⁸ PFU release within 8 h. Poor phage release (7 × 10⁵-4 × 10⁷ PFU) was observed in 5% HPMC, 5% HEC and 30% HPC gels. The biostability of the optimized hydrogels was phage-specific with less titer loss observed for PEV1 (0-0.8 log) than for PEV31 (0.3-1.4 log). Both phages remained stable in PEO, PVA and HPMC hydrogels with <1 log titer reductions when stored at 5 °C. This study showed that 7.5% PEO and 20% PVA hydrogel formulations could be promising therapeutic systems for delivering phages for the treatment of wound infections.