A Perspective on Microbubble Systems for Infectious Microenvironment Restoration and Antibiotic Delivery

Multidrug-resistant (MDR) bacterial infections frequently occur in hostile microenvironments marked by acidic pH, hypoxia, oxidative stress, and biofilm formation—conditions that reduce antibiotic efficacy. While isolated attempts to restore individual microenvironmental factors, such as pH or oxygenation, have shown promise, they rarely address the full spectrum of physicochemical disruptions at infection sites. This work proposes a new strategy: the use of a programmed cocktail of microbubbles, with each population individually loaded with a distinct restorative agent (e.g., pH buffer, oxygen donor, redox modulator) and designed for ultrasound activation at the infection site. Optionally, these microbubbles may be targeted using antibodies to enhance site specificity. This modular approach enables the selective reprogramming of multiple aspects of the infectious microenvironment in situ, thereby improving the efficacy of subsequent or concomitant antibiotic action. In critically ill patients with MDR infections, even modest improvements in local drug performance may be decisive for clinical outcomes. By integrating developments in microbubble engineering, ultrasound-triggered release, and microenvironment modulation, this article outlines a potential path forward in adjunctive therapy for challenging bacterial infections.