Cell membrane-coated berberine-dipotassium glycyrrhizinate nanomaterials for treating pulmonary infections following craniofacial surgery

Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen in local and pulmonary infections following craniofacial surgery, and antibiotic resistance can significantly hinder patient recovery. Berberine, a broad-spectrum antibacterial agent from traditional Chinese medicine, has been clinically used for decades but suffers from low bioavailability. Metal-organic frameworks (MOFs), with their high surface area and porosity, enable high drug loading and targeted release under specific conditions but are rapidly cleared from circulation. By coating MOFs with macrophage membranes, immune-evasion signals are mimicked, reducing clearance rates. This cell membrane-coated MOF drug delivery system allows berberine to specifically target infected areas, evade phagocytosis, and effectively combat infections. Using a one-pot synthesis method, zeolitic imidazolate framework-8 (ZIF-8) co-loaded with berberine and glycyrrhizinate (Ber&Gly@ZIF-8) was synthesized and coated with RAW 264.7 macrophage membranes to form Ber&Gly@ZIF-8@CM (BGZC). The nanomaterials were characterized using dynamic light scattering, ultraviolet spectrophotometry, Fourier-transform infrared spectroscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, and transmission electron microscopy. Antibacterial activity against MRSA was tested via colony forming unit (CFU), live/dead staining, and electron microscopy. Cytocompatibility was assessed via hemolysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. A murine lung infection model evaluated targeting and therapeutic efficacy. The average particle size of BGZC was approximately 200 nm. At a concentration of 100 µg/mL, the material exhibited a 99.5% bactericidal efficacy. The hemolysis rate was less than 5%, and at a concentration of 50 µg/mL, the survival rate of human normal lung epithelial cells (BEAS-2B) exceeded 90%. Additionally, the internalization rate of the material by RAW 264.7 cells was 10.88%, which was lower than the 22.56% observed in the group without cell membrane coating. In infected mice, BGZC accumulated in inflamed lungs, reducing bacterial load and consolidation without systemic toxicity (normal blood parameters and organ histology). Uninfected mice showed liver-focused accumulation. BGZC exhibits excellent targeting ability for infections and good biocompatibility, effectively reducing bacterial load and alleviating lung inflammation. It shows potential for treating local and pulmonary infections following craniofacial surgery. This macrophage-coated MOF nanoplatform enables targeted, biocompatible delivery of berberine, offering a promising strategy for treating drug-resistant infections after craniofacial surgery with reduced systemic toxicity. • A macrophage membrane-coated MOF drug delivery system (BGZC) was developed to enhance berberine’s bioavailability and infection-targeting ability. • BGZC effectively evades immune clearance and targets MRSA-infected tissues, showing strong antibacterial efficacy (99.5% at 100 µg/mL). • The nanocarrier demonstrates excellent biosafety, with < 5% hemolysis and > 90% BEAS-2B cell viability at therapeutic concentrations. • This study presents a promising strategy for treating antibiotic-resistant pulmonary infections post-craniofacial surgery using biomimetic nanotechnology.