Bacteria-targeting liposomes for enhanced delivery of cinnamaldehyde and infection management

Schematic illustration of the P-CA-Lipo preparation and anti-infection effect. The PMB-modified, CA-loaded liposomes were developed. P-CA-Lipo could interact with the bacterial membrane and destroy the LPS barrier, subsequently promoting the CA delivery. In addition, P-CA-Lipo was capable of neutralizing LPS during infection. These effects coordinately promoted infection management. [Display omitted] •Development of polymyxin B-modified liposome (P-Lipo) with gram-negative bacterial targeting effect and LPS-neutralization effect.•P-Lipo can interact with the bacterial membrane to enhance cinnamaldehyde delivery, which leads to superior antibacterial effect.•The two-pronged attack strategy of the developed P-Lipo can synergistically inhibit bacteria and inflammation. Drug-resistant gram-negative bacteria have emerged as a global crisis. Therefore, novel antibiotics and novel anti-infection strategies are urgently needed. Current antibiotics remain unsatisfactory due to poor targeting efficiency and poor drug penetration through the bacterial cell wall. Thus, targeted delivery of antibiotics into gram-negative bacteria should be a promising approach. Moreover, gram-negative bacteria can release lipopolysaccharide (LPS) to induce inflammatory response and septic shock, further increasing the disease burden. Hence, it is also promising to neutralize LPS while delivering antibiotics. This study aims to develop a multifunctional bacteria-targeting liposome that could enhance the delivery of antibiotics and adsorb LPS. A polymyxin B (PMB)-modified liposomal system (P-Lipo) was developed as novel carrier of cinnamaldehyde (CA) by using a thin-film evaporation method. Liposome morphology, size, zeta potential, stability, entrapment efficiency, and in vitro release were systematically evaluated. The bacteria-targeting effect and LPS-neutralizing capacity of P-Lipo were evaluated both in vitro and in vivo. The antibacterial effect of CA-loaded P-Lipo was assessed in Escherichia coli (E. coli) O157:H7 and Pseudomonas aeruginosa (P. aeruginosa). Ultimately, the therapeutic effect of P-CA-Lipo was investigated in E. coli O157:H7-infected mice. P-Lipo was successfully synthesized and encapsulated with CA, which was well characterized. Both in vivo and in vitro experiments demonstrated that P-Lipo could efficiently target the E. coli after modification with PMB. Compared with free CA, CA-Lipo, and P-Lipo, P-CA-Lipo exhibited a significantly enhanced inhibitory effect on E