Nanostructure Control of an Antibiotic-Based Polyion Complex Using a Series of Polycations with Different Side-Chain Modification Rates

Developing nanovehicles for delivering antibiotics is a promising approach to overcome the issue of antibiotic resistance. This study aims to utilize a polyion complex (PICs) system for developing novel nanovehicles for polymyxin-type antibiotics, which are known as last resort drugs. The formation of antibiotic-based PIC nanostructures is investigated using colistimethate sodium (CMS), an anionic cyclic short peptide, and a series of block catiomers bearing different amounts of guanidinium moieties on their side chains. In addition, only the modified catiomer, and not the unmodified catiomer, self-assembles with CMS, implying the importance of the guanidine moieties for enhancing the interaction between the catiomer and CMS via the formation of multivalent hydrogen bonding. Moreover, micellar and vesicular PIC nanostructures are selectively formed depending on the ratio of the guanidine residues. Size-exclusion chromatography reveals that the encapsulation efficiency of CMS is dependent on the guanidinium modification ratio. The antimicrobial activity of the PIC nanostructures is also confirmed, indicating that the complexation of CMS in the PICs and further release from the PICs successfully occurs.

Automated summary

This study develops novel nanovehicles for polymyxin-type antibiotics using a polyion complex (PICs) system. The importance of guanidine moieties in enhancing the interaction between catiomer and colistimethate sodium (CMS) is demonstrated. The ratio of guanidine residues determines the formation of micellar or vesicular PIC nanostructures. The encapsulation efficiency of CMS depends on the guanidinium modification ratio.