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Celebrated project can meet the threat of antibiotic resistance

When bacteria develop a defence against antibiotics, new solutions must be found. An EU-financed project under the leadership of RISE has succeeded in demonstrating that peptides may be one such solution. “The results point the way towards the development of new antibiotic preparations,” says Lovisa Ringstad, project manager of FORMAMP.

Antibiotic resistant bacteria are a growing problem. Infections that might once have been easily treated now require greater efforts. Diseases that were previously treated as a matter of routine can cause serious harm – or even prove fatal.

According to the WHO, during 2016, 600,000 people were infected by multi-resistant bacteria, resulting in 240,000 deaths.

In the United States alone, Meticillinresistent Staphylococcus aureus (MRSA), which is common in hospital environments, costs society over $3 billion annually.

It was against this background that the EU decided to finance FORMAMP.

Five countries in cooperation

With 16 partners from five countries, FORMAMP is a four year project. The acronym consists of the two important components FORM (formulation) and AMP (antimicrobial peptides).

“What we have done is to systematically test various methods for delivering peptides to the infected area in the lungs or skin. This has not been done previously on anything like the scale and scope of our project,” says Lovisa Ringstad.

Antimicrobial peptides are part of the body’s own defence against bacteria. They are short protein chains that act quickly to make it difficult for bacteria to develop resistance. There is nothing new in the fact that these peptides are able to kill bacteria; however, the problem has been in delivering them to the core of infection before they breakdown.

This is where the project’s focus on nanoformulation comes in. Five different carriers have been tested, all with their specific advantages for delivering peptides to the desired location. Lipid particles, for example, have advantages for dermal application, using microgels it is possible to control release, while mesoporous silica has proved to be well-suited to inhalation treatment.

“We tested one peptide against tuberculoses with excellent results when formulated together with our carrier; in fact, with better results than we anticipated – and the nanocarrier reinforced the effect,” says Lovisa Ringstad.

Foundation for continued research

Thus far, the project has resulted in 14 scientific publications, a number of patents, the licensing of a peptide owned by one of the project partners for further development of products for treating skin infections and, not least, laid the foundations for continued cutting-edge research.

“Our goal throughout the project has been to develop new concepts that lead to growth for the participating companies, including through opportunities to apply for new patents. We have also carried out the regulatory groundwork in preparation for future clinical studies of the most successful formulations developed within the project. We have been careful to participate in conferences and get information about the research across to a broad audience, with over 50 presentations so far,” explains Lovisa Ringstad.

RISE has project managed the collaboration. With consideration for its scope, FORMAMP was organised into specific work packets at an early stage in order to focus the work.

“We have worked with clear objectives as a prerequisite for the collaboration. Coordination is important and active project management has been demanded. We have set, and met, tight deadlines. The process has been eased by the entire consortium meeting twice a year, facilitating personal contacts at various levels.”

In addition to project management, RISE has been able to call on expertise in a number of research fields, including nanoformulation and pulmonary carriers. RISE has also led a good deal of the impact testing, toxicological evaluation, upscaling and regulatory work.

Success story according to EU Commission

FORMAMP was recently acknowledged and highlighted by the EU Commission as a success story. For RISE, the ripples of the project are already clear.

“Over the course of the journey, interest in resistant bacteria has increased in society at large, with many people becoming aware of the issue beyond the confines of scientific journals. For our part, FORMAMP has also allowed us to focus on the skills we have at our disposal – something that will ease the way for future project applications.”

A large amount of this knowledge is now being funnelled into the Vinnova-financed project NextBioForm, in which work will be directed towards improving the preparation and production of biopharmaceuticals.

This is a freestanding project but even here we have benefited from the work carried out in FORMAMP,” says Lovisa Ringstad.


Nanoformulation

Formulation is all about creating the best possible unit from multiple components. In terms of pharmaceuticals, the challenges include finding the correct amount of the active substance, the right form of distribution (e.g. tablet, cream), creating the right balance of ingredients to ensure that the active substance has the desired effect in the right location, and so on. All in order to achieve the optimal effect and to ensure that the drug is safe for use by patients.

The task of nanoformulation is the same, although it uses extremely small structures. One nanometre is one billionth of a metre – or the length of three gold atoms lined up. FORMAMP has utilised particles of these miniscule dimensions to create peptide carriers.