Bacterial membrane vesicles as novel nanosystems for drug delivery.

Bacterial membrane vesicles (BMVs) are closed spherical nanostructures that are shed naturally and ubiquitously by most bacterial species both in vivo and in vitro. Researchers have elucidated their roles in long-distance transport of a wide array of cargoes, such as proteins, toxins, antigens, virulence factors, microbicidal agents and antibiotics. Given that these natural carriers are important players in intercellular communication, it has been hypothesized that they are equally well attuned for transport and delivery of exogenous therapeutic cargoes. Additionally, BMVs appear to possess specific properties that enable their utilization as drug delivery vehicles. These include their ability to evade the host immune system, protection of the therapeutic payload and natural stability. Using bioengineering approaches, BMVs have been applied as carriers of therapeutic moieties in vaccines and for targeted delivery in cancer. In this article, we explore BMVs from the perspective of understanding their applicability to drug delivery. BMV biology, including biogenesis, physiology and pathology, is briefly reviewed. Practical issues related to bioprocessing, loading of therapeutic moieties and characterization for enabling scalability and commercial viability are evaluated. Finally, challenges to clinical translation and rational design approaches for novel BMV formulations are presented. Although the realization of the full potential of BMVs in drug delivery hinges on the development of scalable approaches for their production as well as the refinement of targeting and loading methods, they are promising candidates for development of a novel generation of drug delivery vehicles in future.