Size-controlled antimicrobial peptide drug delivery vehicles through complex coacervation

Due to the escalating threat of the pathogens' capability of quick adaptation to antibiotics, finding new alternatives is crucial. Although antimicrobial peptides (AMPs) are highly potent and effective, their therapeutic use is limited' as they are prone to enzymatic degradation, are cytotoxic and have low retention. To overcome these challenges, we investigate the complexation of the cationic AMP colistin with diblock copolymers poly(ethylene oxide)-<i>b</i>-poly(methacrylic acid) (PEO-<i>b</i>-PMAA) forming colistin-complex coacervate core micelles (colistin-C3Ms). We present long-term stable kinetically controlled colistin-C3Ms that can be prepared from several block lengths of PEO-<i>b</i>-PMAA polymers, where the polymerisation degree governs the overall micellar size. To achieve precise control over size and polydispersity, which are crucial for drug delivery applications, we investigate the hybridisation of PEO-<i>b</i>-PMAA polymers with varying chain lengths or PMAA homopolymers in ternary complex coacervation systems with colistin. This results in size-tunable colistin-C3Ms, ranging, depending on the mixing ratios, from micellar sizes of 26 nm to 100 nm. With size tunability at rather narrow size distributions and high stability, ternary colistin-C3Ms offer potential advancements in C3M drug delivery, paving the way for more effective and targeted treatments for bacterial infections in precision medicine.