Professor Maike Windbergs and her team at Goethe University Frankfurt have developed a revolutionary approach to treating chronic wounds using bacteriophage-loaded dressings, representing a significant advancement in targeted drug delivery systems.
The innovative wound dressing appears deceptively simple—light-colored and soft to the touch—but contains sophisticated ultrafine fibers approximately one-fiftieth the thickness of human hair. These fibers feature a complex core-shell structure with an outer layer of polyvinylpyrrolidone (PVP) encapsulating bacteriophages, viruses that specifically target bacteria without affecting human cells.
Advanced Manufacturing Through Electrospinning
The wound dressings are manufactured using a process called electrospinning, where several thousand volts are applied between a nozzle and rotating spindle. As the polymer solution exits the nozzle, it's drawn toward the oppositely charged spindle, creating ultrafine fibers as the solvent evaporates.
"Our special spinneret enables us to embed the bacteriophages in the fibers during this process," explains Windbergs, who heads the Institute of Pharmaceutical Technology at Goethe University Frankfurt.
When applied to wounds, these dressings gradually release bacteriophages over hours or days, providing sustained antimicrobial activity against bacteria that impede healing. "Even resistant species are no match for this," Windbergs notes. "The high-tech dressings thus represent a promising approach for bringing wounds under control that can hardly be treated clinically."
The Science of Targeting in Drug Delivery
Windbergs, who has specialized in drug carriers since completing her doctoral studies at Heinrich Heine University Düsseldorf, explains that effective drug delivery relies on "targeting"—ensuring medications reach their intended site of action and function optimally once there.
Targeting strategies fall into two main categories: passive and active. "Passive targeting means that we make use of certain properties of the diseased tissue to enrich the active substance," Windbergs explains. For instance, wound infections create distinct microenvironments where bacteria lower the pH and release metalloproteases that cleave proteins and worsen inflammation.
These altered conditions can be exploited by designing carriers that respond specifically to these environmental changes. "We can make targeted use of this phenomenon—for example by packaging active substances in a carrier that dissolves particularly quickly at a low pH value or which metalloproteases can easily cleave," says Windbergs.
Active targeting takes precision a step further by directing drugs to specific cells or molecules using molecular "address labels," often antibodies that bind to specific target structures. The two approaches can be combined for enhanced efficacy.
Customized Approaches for Different Therapeutics
Each therapeutic agent requires its own tailored delivery strategy. Windbergs points to RNA vaccines against SARS-CoV-2 as an example: "They were packaged in lipid nanoparticles, in lay terms small fatty spheres." The positive charge of these lipids not only encapsulates the negatively charged RNA but also activates the immune system—a desired effect for vaccines.
However, when RNA molecules are used to treat existing diseases rather than prevent them, a strong immune response may be counterproductive. "To prevent this, we have to find a completely different type of packaging," Windbergs explains.
Laboratory-Cultivated Human Tissues as Testing Platforms
To validate these drug delivery systems, Windbergs' team utilizes both donated human tissue from surgical procedures (with patient consent) and laboratory-cultivated human tissues.
One particularly significant model is their blood-brain barrier system. This complex barrier, which prevents harmful substances from entering the brain from the bloodstream, consists of specialized endothelial cells working in conjunction with other cell types like microglia.
"Despite its complex structure, it is meanwhile possible to cultivate the blood-brain barrier in the laboratory from different cell types," Windbergs explains. "And not just the blood-brain barrier of healthy people but also of people with neurodegenerative diseases such as Alzheimer's."
This capability is crucial for understanding how the barrier becomes more permeable in neurodegenerative conditions—possibly due to amyloid plaque fragments—and for developing strategies to deliver therapeutics to affected brain regions despite the barrier.
Creating Physiologically Relevant Test Systems
Cultivating these complex tissues requires precise protocols tailored to each tissue type. Components must often be pre-cultivated separately under specific conditions before being combined according to strict rules.
To achieve physiologically relevant models, cultivation conditions must closely mimic those in the human body. For instance, when growing small intestine mucous membrane, the culture medium must be agitated to form the characteristic tissue folds. "The cells need a certain degree of mechanical shear stress," Windbergs explains, "but the amount is very important: If the culture is subjected to excessive mechanical stress, the cells die."
While developing these systems requires significant effort, the resulting human cell-based models provide valuable alternatives to animal testing and more relevant data for human applications.
Future Implications for Pharmaceutical Development
The targeting strategies and testing systems developed by Windbergs' team represent significant advancements in pharmaceutical technology with broad implications. By enabling more precise drug delivery, these approaches can increase therapeutic efficacy while reducing side effects and treatment costs.
For chronic wounds and other difficult-to-treat conditions, the bacteriophage-loaded dressings offer a promising alternative to conventional treatments, particularly for infections involving antibiotic-resistant bacteria.
As pharmaceutical development continues to advance toward more personalized and targeted approaches, the work of Windbergs and her team exemplifies how innovative delivery systems and physiologically relevant testing platforms can accelerate the development of more effective therapeutics.
