Chlorhexidine polyphosphates: mechanistic aspects and orthopaedic applications

Chlorhexidine polyphosphates are sparingly soluble salts of the broad-spectrum antiseptic, chlorhexidine (CHX). CHX is widely used in medicinal products and medical devices including catheter securement devices, mouthwashes, and topical skin disinfectants prior to surgical procedures. Due to its non-specific mechanism of action, the chance of microbes becoming resistant to CHX is much lower than for antibiotics. However, current CHX-based treatments contain CHX digluconate, which is highly water soluble. After application, the CHX is rapidly released and washed away, meaning the treatments must be regularly reapplied to maintain the required dose. This is undesirable.
CHX polyphosphates are produced by Pertinax Pharma (a University of Bristol spin-out company and industrial sponsor of this project) and can be incorporated into various substrates used in medical devices. When placed in an aqueous environment, CHX polyphosphates slowly release CHX over a sustained period, overcoming the limitations associated with CHX digluconate. The release can be also tuned for different applications depending on the formulation and substrate.
Currently, the underlying mechanism which determines CHX release under different conditions is not fully elucidated. This project will begin with physicochemical characterisation of selected CHX polyphosphates, including determining solubility products, identifying the phosphate species present at equilibrium and ultimately determining the mechanism(s) that control CHX release. Interactions of phosphates and CHX polyphosphates on model cell membranes and vesicles will also be investigated. This work will aim to establish whether phosphate ions affect the antimicrobial efficacy of CHX when released from CHX polyphosphates.
The remainder of the project will focus on applying CHX polyphosphates for use in a new generation of orthopaedic materials. Antibiotic-laced orthopaedic materials are widely used to prevent and treat infections associated with joint replacement, but antibiotic resistance in the pathogens associated with these infections is rendering these materials less effective and infections harder to treat. The CHX polyphosphate orthopaedic materials offer an opportunity to circumvent the need for antibiotics by using antiseptic to suppress infection during the post-surgical period. This will include studying the release of CHX from these substrates and the resulting antimicrobial efficacy, biocompatibility and toxicity, comparing to existing commercial products.