Bacteria as drug delivery vehicles

Abstract

Both chemotherapy for cancer treatment and antibiotic therapy for bacterial infections require systemic applications of the drug and a systemic application is always linked to a number of disadvantages. To circumvent these a targeted drug delivery system was developed. It utilizes the ability of phagocytes from the hosts own immune system to recognize and internalize antigens. Deactivated M. luteus, a non-pathogenic gram positive bacteria was loaded with high concentrations (exceeding the IC50 at least 60 fold in local intracellular concentration) the chemotherapeutics doxorubicin or DP44mt or with the bactericidal chlorhexidine. The modified bacteria is fed to phagocytes (Monocytes/Macrophages or neutrophils) and serves as protective shell for the transporting and targeting phagocyte. The phagocyte is recruited to the tumor site or site of infection and releases the drug along with the processed M. luteus via the exosome pathway upon arrival. The chlorhexidine drug delivery system was successfully tested both in vitro and in vivo, reducing the pathogen count and preventing systemic spread of a F. necrophorum infection in a mouse model. The doxorubicin drug delivery system reduced the viability of 4T1 cancer cells to 20% over the course of four days in vitro.