Antimicrobial lipids in nano-carriers for antibacterial delivery

Lipid Nanoparticle Technology for Delivering Biologically Active Fatty Acids and Monoglycerides

“…count in the treated group [ 154 ]. While such efforts are promising in the sense that biologically active fatty acids and monoglycerides are reaching human clinical trials, the results also highlight probably the biggest obstacle in the translation of fatty acids and monoglycerides to everyday clinical practice–the outstanding need to develop more relevant and predictive in vitro models for preclinical assessment and validation of the activity and safety of developed (nano)formulations [ 16 ].…”

“…Practically, this means they are only active at sufficien high concentrations, at which they begin to self-assemble into micellar nanostructur However, such micelles readily lose structure upon dilution and fatty acid and mon glyceride monomers are mainly inactive. The translation of fatty acids and monoglyc ides into clinically feasible therapies is further challenged by formulation hurdles caus by low aqueous solubility and dispersibility [16,19]. To address these issues, there h been extensive attention placed on developing lipid nanoparticle technologies to enca sulate biologically active fatty acids and monoglycerides and there are several compelli reasons to do so: (1) stable supramolecular structures enable biological functionality fatty acids and monoglycerides along with improving dispersibility; (2) nanoscale size ideal for interfacing with biological targets such as bacterial cells and virus particles; a (3) additionally, nanoscale size enables the potential for cellular uptake, which could le to fatty acids and monoglycerides exhibiting both intracellular and extracellular activiti Moreover, lipid nanoparticles are the most common class of FDA-and EMA-a proved nanomedicines [20], representing a technological platform that offers an asso ment of modifiable features such as size, shape, charge, surface properties (including l and presentation), and responsiveness that can be engineered to increase cargo loadi capacity, chemical stability, and capability to cross various biological barriers dependi on the application context.…”

“…However, such micelles readily lose structure upon dilution and fatty acid and monoglyceride monomers are mainly inactive. The translation of fatty acids and monoglycerides into clinically feasible therapies is further challenged by formulation hurdles caused by low aqueous solubility and dispersibility [ 16 , 19 ]. To address these issues, there has been extensive attention placed on developing lipid nanoparticle technologies to encapsulate biologically active fatty acids and monoglycerides and there are several compelling reasons to do so: (1) stable supramolecular structures enable biological functionality of fatty acids and monoglycerides along with improving dispersibility; (2) nanoscale size is ideal for interfacing with biological targets such as bacterial cells and virus particles; and (3) additionally, nanoscale size enables the potential for cellular uptake, which could lead to fatty acids and monoglycerides exhibiting both intracellular and extracellular activities.…”

“…Hence, practically realizing therapeutic delivery of fatty acids and monoglycerides calls for the development of effective pharmacological strategies to encapsulate fatty acids and monoglycerides in configurations that not only support high loading capacity but also permit retention, or even enhancement, of membrane-modulating biological activities. These design requirements have led to the development of numerous, increasingly sophisticated nano-carriers to encapsulate and deliver fatty acids and monoglycerides [ 16 , 17 ], a topic of nanomedicine that is experiencing a renaissance in general due to the widespread implementation of lipid nanoparticle technology for vaccine delivery applications [ 18 ] and the broader translational possibilities that such developments inspire.…”

Nano- and Macroscale Imaging of Cholesterol Linoleate and Human Beta Defensin 2-Induced Changes in Pseudomonas aeruginosa Biofilms

“…We have previously demonstrated the broad-spectrum activity of liposomal formulations of various fatty acids and cholesteryl esters, including CL [ 31 ]. The ability of liposomes to deliver antibiotics inside microbial biofilms make them worth considering for treating recalcitrant biofilm-mediated infections, such as those caused by PA in cystic fibrosis [ 44 , 45 , 46 ].…”