Advances in Dendrimer-Based Anti-Infective Systems: In Vivo Insights and Perspectives.

The rise of antimicrobial resistance and the persistence of difficult-to-treat infections have stimulated interest in new strategies to overcome these problems. Among these strategies, dendrimers, which are highly branched monodisperse macromolecules, have emerged as innovative antimicrobial and anti-infective platforms. Dendrimers can act as intrinsic antimicrobial agents through multivalent interactions or membrane disruption or serve as nanocarriers for antibiotics, antiviral agents, antibiofilm compounds, gas-releasing active molecules, or photosensitizers. This review analyzes dendrimer-based anti-infective systems for which in vivo or clinical evaluation has been reported. The literature covers diverse platforms, including PAMAM, poly(L-lysine), peptide, carbosilane, phosphorhydrazone, polyglycerol, polyester, and other dendritic architectures. The available evidence includes infected animal models, pharmacokinetic and biodistribution studies, local tolerance studies, and clinical trials. PAMAM systems are the most extensively explored preclinically, whereas poly(L-lysine) dendrimer astodrimer/SPL7013 remains the most clinically advanced example. Overall, dendrimers provide a chemically tunable and biologically versatile approach to anti-infective research, but the current evidence remains heterogeneous. Direct comparison across studies is limited by differences in dendrimer scaffold, generation, surface chemistry, formulation, pathogen, infection model, administration route, dosing regimen, and biological endpoint. Future development will require better-defined in vivo models, more systematic safety and biodistribution studies, clearer structure-activity relationships, and stronger links between in vitro activity and clinically relevant efficacy.