Formulation of three tailed bacteriophages by spray-drying and atomic layer deposition for thermal stability and controlled release.

Deep infection is the second most common complication of arthroplasty following loosening of the implant.1 Antibiotic-loaded bone cements (ALBCs) and high concentrations of systemic broad-spectrum antibiotics are commonly used to prevent infections following injury and surgery. However, clinical data fails to show that ALBCs are effective against deep infection, and negative side effects can result following prolonged administration of antibiotics.2,3 Additionally, the rise of multidrug resistant (MDR) bacteria provides an urgent need for alternatives to broad-spectrum antibiotics.4 Phage therapy, or the use of bacteriophages (viruses that infect bacteria) to target pathogenic bacteria, might offer a safe alternative to combat MDR bacteria.5 Application of phage therapy in the setting of deep infections requires formulation strategies that would stabilize bacteriophage against chemical and thermal stress during bone-cement polymerization, that maintain bacteriophage activity for weeks or months at physiological temperatures, and that allow for sustained release of phage to combat slow-growing, persistent bacteria. Here, we demonstrate the formulation of three phages that target diverse bacterial pathogens, which includes spray-drying of the particles for enhanced thermal stability at 37°C and above. Additionally, we use atomic layer deposition (ALD) to coat spray-dried powders with alumina to allow for delayed release of phage from the dry formulations, and potentially protect phage against chemical damage during bone cement polymerization. Together, these findings present a strategy to formulate phages that possess thermal stability and sustained release properties for use in deep infections.

Demonstration of Tunable Control over a Delayed-Release Vaccine Using Atomic Layer Deposition.

Many vaccines require multiple doses for full efficacy, posing a barrier for patient adherence and protection. One solution to achieve full vaccination may be attained with single-administration vaccines containing multiple controlled release doses. In this study, delayed-release vaccines were generated using atomic layer deposition (ALD) to coat antigen-containing powders with alumina. Using in vitro and in vivo methods, we show that increasing the coat thickness controls the kinetics of antigen release and antibody response, ranging from weeks to months. Our results establish an in vitro-in vivo correlation with a level of tunable control over the antigen release and antibody response times with the potential to impact future vaccine design.