Antimicrobial peptide dendrimers assisted Nanocomposite-Loaded lyotropic liquid crystalline for multimodal surgical site infection management

Abstract

Superficial incisional surgical site infections (SISSIs) were a serious challenge leading to delayed wound healing and even systemic diseases. The high incidence of antibiotic resistance and unprotected wound lesions severely hindered the current therapeutical efficiency. In this study, an antibacterial nanocomposite PAMAM-PLL@AuNPs was designed to avoid antibiotic resistance, and a lyotropic liquid crystal system was used for local drug delivery and protecting lesions. The PAMAM-PLL was constructed with polyamide amine (PAMAM) as the core and polylysine (PLL) as the branch chain, which increased the antibacterial activity by 4 times. After being connected to gold nanoparticles (AuNPs), a further 2 times antibacterial activity improvement was achieved. PAMAM-PLL@AuNPs could eliminate bacteria by multimodal mechanisms, including causing leakage of intracellular substances, inducing intracellular reactive oxygen species and inhibiting bacterial metabolism. Thanks to their spontaneous phase transition and the mechanical response characteristics of the lattice structure, lyotropic liquid crystal with self-healing characteristics was employed to load PAMAM-PLL@AuNPs. The unique structure facilitated buffering external forces and accelerated wound healing. The excellent antibacterial and wound healing properties of the lyotropic liquid crystal drug delivery system were confirmed by a surgical incision infection model. This study is expected to provide a robust strategy for the treatment of SISSIs.