Liposomes-Based Drug Delivery Systems of Anti-Biofilm Agents to Combat Bacterial Biofilm Formation

Abstract

All currently approved antibiotics are being met by some degree of resistance by the bacteria they target. Biofilm formation is one of the crucial enablers of bacterial resistance, making it an important bacterial process to target for overcoming antibiotic resistance. Accordingly, several drug delivery systems that target biofilm formation have been developed. One of these systems is based on lipid-based nanocarriers (liposomes), which have shown strong efficacy against biofilms of bacterial pathogens. Liposomes come in various types, namely conventional (charged or neutral), stimuli-responsive, deformable, targeted, and stealth. This paper reviews studies employing liposomal formulations against biofilms of medically salient gram-negative and gram-positive bacterial species reported recently. When it comes to gram-negative species, liposomal formulations of various types were reported to be efficacious against Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and members of the genera Klebsiella, Salmonella, Aeromonas, Serratia, Porphyromonas, and Prevotella. A range of liposomal formulations were also effective against gram-positive biofilms, including mostly biofilms of Staphylococcal strains, namely Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus saprophyticus subspecies bovis, followed by Streptococcal strains (pneumonia, oralis, and mutans), Cutibacterium acnes, Bacillus subtilis, Mycobacterium avium, Mycobacterium avium subsp. hominissuis, Mycobacterium abscessus, and Listeria monocytogenes biofilms. This review outlines the benefits and limitations of using liposomal formulations as means to combat different multidrug-resistant bacteria, urging the investigation of the effects of bacterial gram-stain on liposomal efficiency and the inclusion of pathogenic bacterial strains previously unstudied.

Nanomedicine against biofilm infections: A roadmap of challenges and limitations

“…Given the legal and ethical framework permitting the use of human tissues, ex vivo models allow a more extensive evaluation of the nanomedicine effectivity in the tissue environment (CD-P-TO, 2022;Pinto et al, 2019;Van Gent et al, 2021). However, such simulations are insufficient for comprehending the in vivo behavior of chronic infections, influenced by various factors like site-specific microbial diversity or environmental conditions (Liu et al, 2019;Makhlouf et al, 2023). Therefore, in vivo models are necessary to see in a more general view the pharmacodynamics, pharmacokinetics and toxicity of the NPs, as well as the immunogenic response at a systemic level (Birk et al, 2021;Fan et al, 2023;Van Gent et al, 2021).…”

“…Therefore, characterizing the physicochemical properties of NPs is essential to determine product stability and storage conditions (Elfadil et al, 2022). Among various nanomaterials, liposomes tend to be less stable, with potential cargo leakage during storage (Al‐Wrafy et al, 2022; Birk et al, 2021; Makhlouf et al, 2023). Conversely, polymer‐based NPs are usually more stable (Al‐Wrafy et al, 2022; Elfadil et al, 2022).…”

“…As a result, only a few biofilm models have successfully incorporated multiple species of microbes, despite the fact that most chronic infections in soft tissues are polymicrobial (Cendra et al, 2019; Cendra & Torrents, 2021; Gabrilska & Rumbaugh, 2015; Li et al, 2021). Besides, prioritizing clinical strains and bacteria with acquired antimicrobial resistance instead of acute‐infectious laboratory strains should be seriously considered (Lebeaux et al, 2013; Liu et al, 2019; Makhlouf et al, 2023). Moreover, most of the in vivo experiments are conducted using young and healthy animals, whereas actual infection often occurs in elderly or immunocompromised patients and, given that biofilms are found in chronic infections, that endure more than the typical 24–48‐h assay duration, experiments should be conducted in a more long‐term.…”

Nano-based drug delivery system for therapeutics: a comprehensive review

“…Modern and advanced synthesis techniques have led to the preparation of a great variety of nanoparticles with different shapes and sizes, together with the use of a great variety of materials [89]. The classification of nanoparticles can be based on other physical and chemical parameters.…”

Liposomal Rifabutin—A Promising Antibiotic Repurposing Strategy against Methicillin-Resistant Staphylococcus aureus Infections

“…In the literature, several examples demonstrate the advantages of using liposomes as drug delivery systems against planktonic and biofilm S . aureus (reviewed in [ 30 , 31 , 32 , 33 ]). Considering the potential of RFB against S .…”