Antimicrobial emulsions: Formulation of a triggered release reactive oxygen delivery system

• Published in: Materials Science & Engineering C 2019-10, Vol.103, p.109735-109735, Article 109735
• Main Authors: Hall, Thomas J., Blair, Jessica M.A., Moakes, Richard J.A., Pelan, Edward G., Grover, Liam M., Cox, Sophie C.
• Format: Article
• Language: English
• Subjects: AMR; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibiotics; Antiinfectives and antibacterials; Antimicrobial; Bacteria - growth & development; CPI; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacology; Emulsion; Emulsions; Formulation; Formulations; Glucose; Glucose oxidase; Gram-negative bacteria; Honey; Hydrogen peroxide; Inversion; Materials science; Oils - chemistry; Oils - pharmacology; Oxidation; Paraffin; Paraffin - chemistry; Paraffin - pharmacology; Paraffins; Polyglycerols; Reactive oxygen species; Reactive Oxygen Species - chemistry; Reactive Oxygen Species - pharmacology; ROS; Shear rate; Shear thinning (liquids); Surgihoney; SurgihoneyRO; Viscosity
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2019.05.020

The enzyme glucose oxidase mediates the oxidation of glucose to produce reactive oxygen species (ROS), such as hydrogen peroxide. This reaction and its products are key to providing honey with its antimicrobial properties. Currently, honey is an adherent, highly viscous product that produces ROS by means of a water-initiated reaction. These properties reduce clinical usability and present a formulation problem for long term stability. This study aims to engineer a water-in-oil emulsion containing an engineered honey (SurgihoneyRO™) that is easy to administer topically and is controllably activated in-situ. Paraffin oil continuous emulsions formulated using the emulsifier polyglycerol polyricinoleate displayed shear-thinning characteristics. Viscosities between 1.4 and 19.3 Pa·s were achieved at a shear rate representative of post-mixing conditions (4.1 s−1) by changing the volume of the dispersed phase (30–60%). Notably, this wide viscosity range will be useful in tailoring future formulations for specific application mechanisms. When exposed to water and shear, these emulsion systems were found to undergo catastrophic phase inversion, evidenced by a change in conductivity from 0 μS in the non-aqueous state, to >180 μS in the sheared, inverted state. Encouragingly, sheared formulations containing ≥50% SurgihoneyRO™ generated sufficient levels of ROS to inhibit growth of clinically relevant Gram-positive and Gram-negative bacteria. This study demonstrates an ability to formulate ROS producing emulsions for use as an alternative to current topical antibiotic-based treatments. Promisingly, the ability of this system to release water-sensitive actives in response to shear may be useful for controlled delivery of other therapeutic molecules. •Delivery of reactive oxygen species produced by a mechanism in engineered honey•Formulation of an oil continuous emulsion to increase ease and control of delivery•Triggered release of active when exposed to water and shear•Demonstrates the ability to inhibit growth of clinically relevant bacteria