Polymyxin Delivery Systems: Recent Advances and Challenges

Abstract

Polymyxins are vital antibiotics for the treatment of multiresistant Gram-negative ESKAPE pathogen infections. However, their clinical value is limited by their high nephrotoxicity and neurotoxicity, as well as their poor permeability and absorption in the gastrointestinal tract. This review focuses on various polymyxin delivery systems that improve polymyxin bioavailability and reduce drug toxicity through targeted and controlled release. Currently, the most suitable systems for improving oral, inhalation, and parenteral polymyxin delivery are polymer particles, liposomes, and conjugates, while gels, polymer fibers, and membranes are attractive materials for topical administration of polymyxin for the treatment of infected wounds and burns. In general, the application of these systems protects polymyxin molecules from the negative effects of both physiological and pathological factors while achieving higher concentrations at the target site and reducing dosage and toxicity. Improving the properties of polymyxin will be of great interest to researchers who are focused on developing antimicrobial drugs that show increased efficacy and safety.

Polymyxins and Bacterial Membranes: A Review of Antibacterial Activity and Mechanisms of Resistance

“…Other efforts are focusing on modified polymyxin formulations or synergistic combinations that decrease toxicity; Yu and colleagues have recently developed an inhalable liposomal mixture of colistin and ciprofloxacin, that showed high effectiveness against P. aeruginosa [ 207 ]. Other interesting formulations of polymyxins are structured gels based on natural and synthetic polymers [ 208 ]. For example, phenylboronic acid polycarbonate hydrogels, that are loaded with polymyxin B, demonstrated in vitro antimicrobial efficacy against P. aeruginosa from burn wound infections [ 209 ].…”

“…A microneedle system composed of sugar, polyvinylpyrrolidone and encapsulated polymyxin B, was developed and used against Salmonella typhimurium , with the achievement of a high antibiotic level in models of porcine skin [ 210 , 211 ]. Innovative delivery systems of polymyxins include microparticles, nanoparticles, liposomes, and niosomes [ 208 ]. A niosome is a non-ionic vesicle comprising a non-ionic surfactant and cholesterol, and can incorporate both hydrophilic drugs (in its aqueous layer) and lipophilic drugs (in its vesicular lipid membrane) [ 212 ].…”

Polypeptide Self-Assembled Nanoparticles as Delivery Systems for Polymyxins B and E

“…A particular focus for these drugs has been the development of delivery systems based on nanoparticles (NPs) of poly(lactide- co -glycolide) [ 15 , 16 ] and chitosan [ 17 ], as well as different poly(methacrylic acid) microgels [ 18 ]. Summaries of different delivery systems available for antibacterial peptide drugs have been presented in some recent reviews [ 19 , 20 , 21 ].…”

Antimicrobial Polymer−Based Assemblies: A Review

“…Several polymyxin formulations have been developed for parenteral use (for treatment of cystic fibrosis, pneumonia, bacteremia, and urinary tract infections), inhalation (cystic fibrosis, pneumonia), and topical use (optic and ophthalmic solutions). The most common polymyxin side effects have been dose−dependent nephrotoxicity and neurotoxicity; since polymyxins were essentially not absorbed by the gastrointestinal tract, their encapsulation into suitable carriers improved intestinal permeability, thereby allowing novel formulations administered by the oral route [ 88 ]. Figure 5 shows a polymer−based formulation for polymyxin B based on the electrostatic attraction between the cationic peptide and the anionic poly (styrene sulphonate) polymer as reproduced from [ 89 , 90 ]; the antimicrobial activity of the polymyxin AMP was influenced by the degree of polymerization of the poly−ion (DP): a low DP improved antimicrobial activity, while a high DP improved the NPs stability [ 89 ].…”