Bacteriophage Encapsulation Using Spray Drying for Phage Therapy.

Abstract

Exploiting the potential of bacteriophages for phage therapy is an exciting future prospect. However, in order to be successful, there is a pressing need for the manufacture of safe and efficacious phage drug products to treat patients. Scalable manufacture of phage biologics as a stable solid dry powder form is highly desirable and achievable using the process of spray drying. Spray drying of purified phage suspensions formulated with suitable excipients can be carried out in a single step with high process throughput and at relatively low cost. The resulting phage-containing powders can possess good storage shelf-life. The process allows control over the final phage dose in the powder and production of microparticles suitable for a variety of therapeutic uses. Spray dried powders may include different polymer formulations employing a multitude of different triggers for phage release at the target site including pH, enzymes, virulence factors etc. The activity of the phages in spray dried powders is adversely affected during spray drying due to dessication and thermal stresses which need to be controlled. The choice of polymers, excipients and moisture content of the dry powders affects the material glass transition temperature and the stability of the phages during storage. The storage temperature and storage humidty are important factors affecting the stability of the phages in the dry powders. A quality by design (QbD) approach for phage drug product development needs to identify drug product characteristics that are critical to quality from the patient's perspective and translates them into the critical quality attributes (CQA) of the drug product. The relationship between the phage drug product CQAs and formulation development and spray drying process conditions are discussed in this article.