A fresh pH-responsive imipenem-loaded nanocarrier against Acinetobacter baumannii with a synergetic effect

Abstract

In recent years, the treatment of Acinetobacter baumannii infections has become a pressing clinical challenge due to its increasing incidence and its serious pathogenic risk. The research and development of new antibacterial agents for A. baumannii have attracted the attention of the scientific community. Therefore, we have constructed a new pH-responsive antibacterial nano-delivery system (Imi@ZIF-8) for the antibacterial treatment of A. baumannii. Due to its pH-sensitive characteristics, the nano-delivery system offers an improved release of the loaded imipenem antibiotic at the acidic infection site. Based on the high loading capacity and positive charge of the modified ZIF-8 nanoparticles, they are excellent carriers and are suitable for imipenem loading. The Imi@ZIF-8 nanosystem features synergistic antibacterial effects, combining ZIF-8 and imipenem to eliminate A. baumannii through different antibacterial mechanisms. When the loaded imipenem concentration reaches 20 µg/mL, Imi@ZIF-8 is highly effective against A. baumannii in vitro. Imi@ZIF-8 not only inhibits the biofilm formation of A. baumannii but also has a potent killing effect. Furthermore, in mice with celiac disease, the Imi@ZIF-8 nanosystem demonstrates excellent therapeutic efficacy against A. baumannii at imipenem concentrations of 10 mg/kg, and it can inhibit inflammatory reaction and local leukocyte infiltration. Due to its biocompatibility and biosafety, this nano-delivery system is a promising therapeutic strategy in the clinical treatment of A. baumannii infections, providing a new direction for the treatment of antibacterial infections.

Targeting the Gut: A Systematic Review of Specific Drug Nanocarriers

“…The protein self-assembles at low pH, promoting the formation of pores in the endosomes, thus enabling endosome escape [ 38 ]. A new pH-responsive nano-delivery system is ZIF-8 [ 137 ], whose NPs showed high loading capacity and positive charge and demonstrated that they were good drug carriers. Moreover, its pH-sensitive behavior allowed this nano-delivery system to guarantee the release of the loaded antibiotic (imipenem) at the acidic infection site.…”

Understanding the biofilm development of Acinetobacter baumannii and novel strategies to combat infection

“…At a concentration of 20 lg/mL, the Imi@ZIF (formed by combining ZIF-8 and imipenem) exhibits antibacterial properties, effectively targeting and eradicating A. baumannii through antibacterial mechanisms. By leveraging the unique properties of Imi@ZIF-8, researchers aim to enhance the efficacy of antimicrobial treatment while minimizing adverse effects associated with conventional therapies [101]. Whereas, Pourhajibagher et al [102] showed that polymeric NPs containing curcumin and nisin, known as CurNisNp, significantly reduce the cell viability of A. baumannii via reactive oxygen species (ROS) generation resulting in significant downregulation of AbaI and csuE expression and biofilm elimination.…”

Tunable Zeolitic Imidazolate Framework‐8 Nanoparticles for Biomedical Applications

“…As we all know, tumor cells are different from normal cells and accompanied with acidic microenvironment due to their abnormal growth. ZIF-8, a non-toxic degradable material which is sensitive to acidic conditions (pH 5.0-6.0) due to protonation effect, [12,13] can not only protect the loading active components from damage in vivo, but also achieve controllable drug release in slightly acidic tumor microenvironment, so that the drugs are accumulated at the tumor region and kill the tumor with high specificity. In other words, ZIF-8 offers a very suitable platform for cancer therapy.…”