Preparation and characterization of transdermal mediated microemulsion delivery of T4 bacteriophages against E.coli bacteria: a novel anti-microbial approach

Abstract

The objective of this study was to design a novel microemulsion system for transdermal delivery of natural antimicrobial agent, i.e. bacteriophage (T4) specifically lysing E. coli bacteria. Pseudoternary phase diagrams were constructed and various formulations were prepared using a combination of ethyl oleate (oil), Tween 80:Span 20 (surfactant mixture) and water (aqueous phase). Developed formulations were subjected to physicochemical characterization, ex vivo and thermodynamic stability studies, skin irritation and histology studies. All the formulations had small droplet size (150–320nm), uniform size distribution (PI < 0.4), adequate viscosity and surface tension. 4 × 105, 6.02 × 106 and 6.7 × 106 PFU/mL was the cumulative amount of bacteriophage permeated from ME1-3, respectively. Results from permeation studies suggested the synergistic effect of oil and surfactant mixture on the permeation profile (p < 0.05), on increasing surfactant concentration with respect to oil, the bacteriophage permeation was increasing and so, the flux was increases too. ME2 was found to be thermodynamically stable, non-irritant and followed zero order kinetics. The bacteriophage viability to lyse E. coli was significantly affected at various temperatures, pH and dilution. Histological findings revealed the effect of formulation variables on the skin, necessary for permeation. These results indicate that microemulsion-based transdermal delivery of bacteriophage can be a promising approach to treat the infections caused by antibiotic-resistant bacteria but needs thorough clinical investigations.