{"id":83534,"date":"2025-05-14T10:00:00","date_gmt":"2025-05-14T08:00:00","guid":{"rendered":"https:\/\/aktuelles.uni-frankfurt.de\/?p=83534"},"modified":"2025-05-02T15:17:12","modified_gmt":"2025-05-02T13:17:12","slug":"right-on-target","status":"publish","type":"post","link":"https:\/\/aktuelles.uni-frankfurt.de\/en\/english\/right-on-target\/","title":{"rendered":"Right on target"},"content":{"rendered":"
New strategies for targeted drug delivery<\/h2>\n\n\n\n
Even the best drug in the world is completely useless if the active substance fails to reach the site of action in the body where it is supposed to fight the disease. Pharmacist Maike Windbergs is an expert in drug carrier systems, whose aim is to ensure targeted delivery. For her research, she also uses human brain, intestinal or skin tissue cultivated in the laboratory.<\/strong><\/p>\n\n\n\n
<\/div>\n\n\n\nElectrospinning: A polymer solution exits a wafer-thin nozzle to which a high voltage has been applied. During the spinning process, actives like therapeutic bacteriophages are embedded directly in the fibers. Photo: AG Windbergs<\/figcaption><\/figure>\n\n\n\n
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The wound dressing is light-colored and as soft as a baby wipe. That it is, in fact, an extremely complex high-tech fabric is invisible to the naked eye, and its fibers are made of something really special.<\/p>\n\n\n\n
Although they are just one-fiftieth the thickness of a human hair, the fibers constitute a sophisticated core-shell structure. Their outer layer consists of a synthetic polymer called polyvinylpyrrolidone (PVP). More interesting, however, is the core encapsulated in the PVP. It contains viruses \u2013 and quite useful ones at that: bacteriophages. These do not infect human cells but instead attack bacteria. This content makes the fabric a beacon of hope for the treatment of chronic wounds.<\/p>\n\n\n\n
The Institute of Pharmaceutical Technology at Goethe University Frankfurt houses the loom used to produce the fabric. It is headed by Professor Maike Windbergs, 44, an expert in delivering active substances against diseases to the place in the body where they are needed. \u201cWe used a process called electrospinning to produce our wound dressings,\u201d she says.<\/p>\n\n\n\n
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High voltage draws polymers apart to form fine fibers<\/h3>\n\n\n\n
In this process, a very high voltage (several thousand volts) is applied to a nozzle and a rotating spindle. The polymer solution exiting the nozzle is attracted by the oppositely charged spindle, which causes the fine jet of liquid to expand. The solvent evaporates at the same time, producing ultrafine fibers that are caught by the rotating spindle. \u201cOur special spinneret enables us to embed the bacteriophages in the fibers during this process,\u201d explains Windbergs.<\/p>\n\n\n\n
When the fabric produced in this way is placed on a wound, the bacteriophages are gradually released. This takes place over hours or even days so that the bacteria preventing the wound from healing are subjected to an ongoing attack over a longer period. \u201cEven resistant species are no match for this,\u201d says Windbergs. \u201cThe high-tech dressings thus represent a promising approach for bringing wounds under control that can hardly be treated clinically.\u201d<\/p>\n\n\n\n
Maike Windbergs has been working on drug carriers since completing her doctoral degree at Heinrich Heine University D\u00fcsseldorf. Drug carriers play an important role in the development of treatment strategies against dangerous diseases: They should not only ensure that drugs reach the site of action in the body but also that these are as effective as possible once they arrive there. In pharmacy, this is also called \u201ctargeting\u201d.<\/p>\n\n\n\n
Targeting is a collective term for various methods that sometimes go hand in hand. \u201cWe differentiate between passive and active targeting,\u201d says Windbergs. \u201cPassive targeting means that we make use of certain properties of the diseased tissue to enrich the active substance.\u201d Wound infections are a good example to illustrate this: The bacteria responsible for such an infection create an environment in which they can thrive particularly well, for example by lowering the pH value in the wound. In addition, certain enzymes, called metalloproteases, are released. These cleave proteins in the infected tissue, which worsens the inflammation.<\/p>\n\n\n\n
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Different conditions prevail in wounds than in healthy skin<\/h3>\n\n\n\n
\u201cThis means that we have a different microenvironment in a wound than we do in healthy skin,\u201d explains Windbergs. \u201cAnd we can make targeted use of this phenomenon \u2013 for example by packaging active substances in a carrier that dissolves particularly quickly at a low pH value or which metalloproteases can easily cleave.\u201d The pathological changes in the tissue ensure that the active substance is released exactly where it is needed.<\/p>\n\n\n\n
Active targeting even goes one step further: It directs the drug systematically to certain cells or even individual molecules that play an important role in the disease. A molecular \u201caddress label\u201d is attached to the carrier, as it were. \u201cThis is often an antibody that binds to specific target structures,\u201d explains Maike Windbergs. The two strategies can also be combined.<\/p>\n\n\n\n
Today, targeting is a very important aspect in the development of new therapeutics because it is possible to achieve a greater effect with a smaller amount of active substance. On the one hand, this makes treatment more cost-effective. In addition, the risk of unwanted side effects is considerably reduced thanks to better targeting accuracy.<\/p>\n\n\n\n
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Customized strategy for each disease<\/h3>\n\n\n\nTests to examine wound healing can be conducted on small pieces of human skin removed during cosmetic surgery, for example. Photo: AG Windbergs<\/figcaption><\/figure>\n\n\n\n
All drugs require their own customized approach. \u201cTake the RNA vaccines developed by BioNTech or Moderna against SARS-CoV-2, for example,\u201d says Windbergs: \u201cThey were packaged in lipid nanoparticles, in lay terms small fatty spheres.\u201d RNA is negatively charged; positively charged lipids can be used to encapsulate the RNA molecules. \u201cThe charge also activates the immune system, which is what a vaccine aims to achieve.\u201d<\/p>\n\n\n\n
Vaccines protect us against infections, but RNA molecules can also be used to cure us of existing diseases. In this case, a strong immune response is not necessarily conducive. \u201cTo prevent this, we have to find a completely different type of packaging,\u201d says Windbergs.<\/p>\n\n\n\n
Drug targeting thus calls for strategies that are not available \u201coff the shelf\u201d, which is why scientists also need suitable test systems to check whether their carriers are fit for the purpose. To do this, the Windbergs Group at the Institute of Pharmaceutical Technology uses human tissue removed during surgery, provided that the patients have given their previous consent. But many are willing to donate. \u201cWe test our wound dressings on skin flaps from operations, for example,\u201d explains Professor Windbergs.<\/p>\n\n\n\n
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Complex tissue \u201creproduced\u201d in the laboratory<\/h3>\n\n\n\n
However, the scientists also use human cells to produce tissue themselves. One example is the blood-brain barrier, which prevents harmful molecules, bacteria or viruses from entering the brain from the bloodstream via the blood vessel walls. To this end, the blood vessels that supply our brain with oxygen and energy are lined with special endothelial cells, which seal the blood vessels and allow only certain substances to pass through. To do this, they work hand in hand with other types of cells \u2013 on the brain side, for example, with the microglia cells, a special type of phagocyte (scavenger cell). Microglia cells can absorb and digest foreign substances and are thus part of the immune system.<\/p>\n\n\n\n
Several other protagonists also play a role in the blood-brain barrier. \u201cDespite its complex structure, it is meanwhile possible to cultivate the blood-brain barrier in the laboratory from different cell types,\u201d explains Windbergs. \u201cAnd not just the blood-brain barrier of healthy people but also of people with neurodegenerative diseases such as Alzheimer\u2019s.\u201d It is now known that this important barrier is damaged in people suffering from such diseases and becomes more permeable. Presumably responsible for this are fragments of amyloid plaques, characteristic deposits of proteins and fat-like molecules found in large numbers in the brains of people with Alzheimer\u2019s disease.<\/p>\n\n\n\n
The Windbergs Group uses the artificial tissue to explore various research questions. \u201cFor example, we reproduce an intact blood-brain barrier in a test tube and then examine what toxic effect certain plaque components have on it,\u201d she explains. This model system is also a helpful tool in the search for strategies to deliver potential active substances to damaged areas of the brain despite the barrier.<\/p>\n\n\n\n
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Creating body-like conditions<\/h3>\n\n\n\n3D model of the human small intestine in which two intestinal cell types were cultivated together: the enterocytes responsible for absorbing nutrients and the goblet cells that produce mucus. The cells were stained and then photographed with the help of a fluorescence microscope. Photo: AG Windbergs<\/figcaption><\/figure>\n\n\n\n
Growing intestinal mucosa, brain tissue or parts of other organs in the laboratory is a complex undertaking. Depending on the type of tissue, different experimental protocols apply and must be followed. Individual components often need to be pre-cultivated separately, each in a special culture medium and under specific conditions. Strict rules apply when mixing them, too: Which type of cell is added when? And in what amount?<\/p>\n\n\n\n
Ideally, the various components then arrange themselves automatically \u2013 just as they would in the human body. \u201cFor this to work, however, cultivation conditions must be exactly right and as similar as possible to those in the organism,\u201d says Windbergs. When cultivating a mucous membrane of the small intestine, for example, the culture medium must be agitated so that the folds typical of this type of tissue are able to form. After all, the digested food that flows through the intestine is also on the move. \u201cThe cells need a certain degree of mechanical shear stress,\u201d continues Windbergs. \u201cBut the amount is very important: If the culture is subjected to excessive mechanical stress, the cells die.\u201d<\/p>\n\n\n\n
The cultivation of human tissue thus calls for a precisely orchestrated procedure. In many cases, the individual steps required for this have been optimized by researchers around the world in many years of work. The effort is nevertheless worthwhile: Scientists can use the organs produced in this way to answer questions for which experiments with animals, for example, would not be particularly promising. After all, a lab mouse is a mouse. Cultivated tissue is something else: It consists entirely of human cells.<\/p>\n\n\n\n
About \/ Maike Windbergs<\/strong>, born in 1980, has been a professor at Goethe University Frankfurt since 2017, where she heads the Institute of Pharmaceutical Technology. Windbergs studied pharmacy in D\u00fcsseldorf and completed her doctoral degree in pharmaceutical technology there and at the universities of Helsinki (Finland) and Enschede (Netherlands). After a research stay at Harvard University in the USA, she was a junior research group leader at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) and at Saarland University, where she completed her Habilitation<\/em> before joining Goethe University Frankfurt. She has received several prestigious scientific awards for her research achievements. windbergs@em.uni-frankfurt.de<\/a><\/p>\n\n\n\nPhoto: Anne Baron<\/figcaption><\/figure>\n\n\n\n
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