Wick, P. | Search bioRxiv

bioRxiv2026

Invisible shield: Sprayable supramolecular antimicrobial microscale films for preventing wound and medical device infections

Wound and device-associated infections remain difficult to eradicate because biofilms block host immunity and antibiotics, accelerating chronicity and resistance. Here, we present a portable, low-cost dual-syringe spray that deposits an ultra-thin, self-assembling antimicrobial film directly on wounds and implant surfaces. The device co-delivers oppositely charged hyaluronic acid (HA) and a cationic antimicrobial peptide (polyarginine, PAR30), which rapidly form a conformal nanometric polyelectrolyte complex at the tissue-material interface. Molecular dynamics simulation revealed pronounced positional heterogeneity within the PAR30/HA complex and identified an N-terminal arginine as a dominant interaction hotspot. The resulting coating adheres to diverse substrates, kills bacteria on contact, prevents biofilm formation, and sustains antimicrobial efficacy. Across vitro assays and murine wound infection models, treatment produced 4 to 5 log reductions in bacterial burden against methicillin-resistant Staphylococcus aureus and Gram-negative pathogens, including Pseudomonas aeruginosa and Escherichia coli. The formulation is biocompatible, did not increase cutaneous inflammation or IL-6 levels in vivo, and reduced post-surgical pain and motor deficits in a mouse incision model. To our knowledge, this is the first antimicrobial treatment system applicable to both tissues and medical devices. Developed under a safe-and-sustainable-by-design approach, this technology combines biocompatible components, nanometric coating for minimal material use, and a simple syringe-based delivery device, offering a scalable, antibiotic-free strategy for wound care and medical device infection prevention. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=173 HEIGHT=200 SRC="FIGDIR/small/717441v1_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@49381aorg.highwire.dtl.DTLVardef@1023e64org.highwire.dtl.DTLVardef@4e282aorg.highwire.dtl.DTLVardef@12eeae4_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Understanding the kinetics of macrophage uptake and the metabolic fate of iron-carbohydrate complexes used for iron deficiency anemia treatment

Iron-carbohydrate complexes (ICCs) are widely used nanomedicines to treat iron deficiency anemia, yet their intracellular fate and the mechanisms of action underlying their differences in treatment outcomes remain poorly understood. Here, we thus performed a comprehensive dynamic characterization of two structurally distinct ICCs - iron sucrose (IS) and ferric carboxymaltose (FCM) - in primary human macrophages, key cells to the iron metabolism. By employing innovative correlative microscopy techniques, elemental analysis, and in vitro pharmacokinetic profiling, we demonstrate that the uptake, intracellular trafficking, and biodegradation of ICCs depend on their physicochemical properties. Specifically, IS is rapidly internalized and processed within endolysosomes, resulting in fast iron release and transient cytotoxicity. Conversely, FCM is sequestered in enlarged endosomes for an extended time before its biodegradation, a phenomenon we term the Hamster Effect, which leads to slower, more sustainable iron release. These results provide unprecedented insights into the metabolic fate of ICCs, enhancing our understanding of their different pharmacokinetic and pharmacodynamic profiles in vivo.

pharmacology and toxicology↗