Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

Abstract

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug's encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.

Keywords: antibiotic; antimicrobial resistance; bacterial infection; liposome.

Figure 1

Schematic representation of different types of liposomes and their major advantages.

Figure 2

Schematic representation of the main advantages of liposomes as antibiotic carriers.

Figure 3

Schematic representation of antimicrobial resistance mechanisms that could be overcome by the use of antibiotic incorporated liposomes. (A) There are several mechanisms of antibiotic resistance, including loss of porins, which reduce the antibiotic entrance; sequestration of the antibiotics by drug binding proteins, blocking its interaction with the target; enzymatic degradation and enzymatic antibiotic modification, which alter the antibiotic making it incapable of inducing its effect; and efflux pumps which expels the antibiotic out of the cell. Blue and yellow spheres indicate antibiotics. The encapsulation of antibiotics provides the delivery of a higher antibiotic concentration within the bacteria infection site possibly stimulating the fusion with the bacterial membrane depending on the lipid composition. By increasing the antibiotic concentration, the resistance mechanisms depicted become obsolete, unable to fully block the antibiotic action. Mechanisms not shown include target modification, target bypass and antibiotic target protection. (B) Liposome penetration in biofilm: biofilms are considered a resistance mechanism due to the lower penetrability of the antibiotic in the extracellular matrix. Antibiotic-loaded liposomes have the ability to interact with bacteria organized in biofilm, enabling the antibiotic delivery within its structure.