[Frontiers in Bioscience 15, 397-417, January 1, 2010]

Drug delivery systems for potential treatment of intracellular bacterial infections

Edurne Imbuluzqueta1, Carlos Gamazo2, Javier Ariza3, Maria J. Blanco-Prieto1

1Department of Pharmacy and Pharmaceutical Technology, University of Navarra, 31080 Pamplona, Spain, 2Department of Microbiology and Parasitology, University of Navarra, 31080 Pamplona, Spain, 3Infectious Disease Service, Hospital Universitario de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Lifestyles of intracellular bacterial pathogens
3.1. Lysis of the intracellular vacuole and escape to the cytosol
3.2. Arrest of phagosome maturation
3.3. Segregation from the endocytic route
3.4. Life within acidic phagosomes
4. Antibiotic treatment of intracellular bacterial infections
5. Antibiotic encapsulation in drug delivery systems
5.1. Liposomes
5.1.1. Uptake of liposomes by mononuclear phagocytic system cells
5.1.2. Intracellular destination of pH-sensitive liposomes
5.1.3. In vitro efficacy of liposome-assisted antibiotic treatment
5.2. Polymeric micro- and nanoparticles
5.2.1. Endocytosis and intracellular fate of particles used as drug delivery systems
5.2.2. Synergy of polymeric particles with cellular bactericidal mechanisms
5.2.3. In vitro efficacy of polymeric particles for antibiotic treatment
6. Treatment of experimental infections mediated by drug delivery systems
6.1. Tuberculosis
6.2. Brucellosis
6.3. Salmonellosis
6.4. Listeriosis
7. Concluding remarks and perspectives
8. Acknowledgment
9. References

1. ABSTRACT

Despite the advent of a considerable number of new antibiotics, treatment of intracellular pathogens still represents a major pharmaceutical challenge. The antibiotic concentration in those specialized niches are often subtherapeutic, for which high doses of antibiotics must often be used. This is not only costly but may also increase localized or systemic side effects. There is therefore an urgent need for materials and methods to enable clinicians to achieve therapeutically effective intracellular concentration of those antibiotics which show good efficiency in vitro. In this setting, the possible use of drug delivery systems (DDS) loaded with antibiotics that exhibit a high in vitro bactericidal activity deserves to be considered. Entrapping or encapsulating the drug within a delivery system provides a greater control of the pharmacokinetic behavior of the active molecule. This more efficient use of antibiotics may diminish their drawbacks and provide the basis for shortening the current time required by classical treatments. This review will focus on the role of DDS as a potential tool against intracellular bacteria.