3D-printed biomimetic liposomal hydrogels for localized and targeted treatment of drug-resistant Candida albicans vaginitis

Abstract

The excessive use of antibiotics has precipitated the emergence of drug-resistant bacterial strains, underscoring the critical need for developing novel, targeted antimicrobial agents. Among the burgeoning class of nanomaterials, silver clusters have attracted considerable attention due to their broad-spectrum and enduring antimicrobial properties, coupled with the crucial advantage of not eliciting resistance. These features render them exceptionally promising in the landscape of antimicrobial therapy. Nevertheless, the constraints associated with the topical application of silver clusters and the adverse effects linked to high-dose shock therapy pose significant challenges that require resolution. To surmount these obstacles, we engineered a sophisticated nanodrug delivery system capable of specific bacterial recognition and synergistic interaction with antimicrobial agents to accomplish precise antibacterial efficacy. Through the interaction between bacterial recognition receptor proteins (TLR2 and TLR4) on macrophage membranes and pathogen-specific molecular patterns on bacteria, we observed that cultivating macrophages in the presence of specific bacteria markedly upregulated the expression of these receptors. We subsequently isolated these specialized membrane proteins, integrated them into liposomes, and loaded silver clusters to formulate composite biomimetic liposomes (Lip@MOMP2@AgNCs). These liposomes can be effectively administered to sites of vaginal infection via intravenous injection, facilitating specific bacterial recognition, and precise targeting. Moreover, we devised a 3D-printed hydrogel mesh scaffold incorporating Lip@MOMP2@AgNCs, which amalgamates the injectable liposomal formulation with the 3D-printed hydrogel scaffold to realize sustained and localized drug release. This investigation not only advances a specific and promising therapeutic strategy for combating drug-resistant Candida albicans vaginitis but also forges new pathways in addressing the formidable challenge of antibiotic resistance.

Keywords

3D printing / Hydrogel / Liposomes / Silver nanoclusters / Vaginitis