Bacterial, viral, and parasitic pathogens can cause a variety of diseases and trigger a hyperinflammatory host responses. This can lead to a cycle of host tissue damage without infection resolution, posing substantial economic and public health burdens. Here, we discuss various drug delivery strategies from the nano to macro scale to mitigate the impact of infection and inflammation. Biological DNA-based matrices such as biofilms and neutrophil extracellular traps can be contributors to infection and inflammation. When engineering drug delivering particles to interface with these biological networks, it is important to consider physicochemical design properties. To this end, we fabricated tunable nanocomplexes co-loaded with silver nanoparticles and tobramycin antibiotic to target bacterial biofilm infection and antimicrobial resistance. These nanocomplexes synergistically inhibited planktonic and biofilm P. aeruginosa growth. By tuning particle composition, we could engineer positively charged nanocomplexes that demonstrated higher interaction with the negatively charged biofilm matrix, providing more effective bactericidal treatment. We then studied how physicochemical design of particles could impact interaction with neutrophil extracellular traps, another DNA-based biological network released from neutrophils in response to infection and can induce hyperinflammation. Similar to our findings with NC-biofilm interactions, we found that positive charge in addition to small size (200 nm) were the main drivers of NET-particle interaction. These findings were leveraged to create DNase-loaded particles that could adhere to NETs at varying degrees and therefore degrade NETs at different rates in vitro. Positively charged, 200 nm DNase-loaded particles showed the highest degree of interaction with NETs and therefore led to faster degradation compared to larger sizes, underscoring the importance of physicochemical design for NET-targeting drug delivery. Finally, we discuss preventative measures to combat infection through delivery of volatile mosquito repellents. We developed polymeric thin film passive emanators that demonstrated sustained release of mosquito repellents over 30 days and tuned release rates through film height and temperature. Overall, these strategies highlight the importance of developing drug delivery methods that target various aspects of the cycle of infection and inflammation to reduce public health burdens.