Electrostatically hindered diffusion for predictable release of encapsulated cationic antimicrobials†

Abstract

A common challenge in infection control is uncontrolled and unpredictable rapid release of antimicrobials – with ramifications on antimicrobial resistance (AMR) development and pollution – that makes it difficult to determine appropriate dosage levels and treatment times. An important class of antimicrobials is surface-active cationic substances, whose charge can be exploited for manipulating both their encapsulation and controlled release. As a proof of concept, the cationic antimicrobial octenidine dihydrochloride (OCT) was encapsulated in a microcapsule matrix of poly(D,L-lactide-co-glycolide) (PLGA) bearing anionic carboxylate end groups. The strong PLGA–OCT interaction was verified by infrared spectroscopy and by comparing the release of OCT to its uptake into empty microcapsules. By expanding a Fickian diffusion model, the binding event was estimated to result in a 10-fold reduction in effective diffusivity resulting in a sustained release maintained for several months. Using this model, the impacts of temperature and release medium solubilizers were globally examined to improve predictability. By exceeding the glass transition temperature of hydrated PLGA, the diffusional release was significantly faster at 37 °C with a diffusivity 200 times that at room temperature. The addition of solubilizers increased the OCT partitioning towards the aqueous phase without affecting its diffusivity.