Category Archives: News

PneumoNP: Exciting 6-month race ahead

With only six months to go before its end, the PneumoNP consortium gathered once more for their penultimate progress meeting on June 20-21, 2017 hosted in the beautiful city of Maastricht by project partner PathoFinder.

During the 1.5-day meeting, the consortium partners discussed the course for the last six months of the project’s duration. The primary goal to bear in mind: to reach the maximum outcome of the project!

Meeting in Maastricht

PneumoNP focuses on the development of a theragnostic system for the treatment of resistant Gram-negative bacterial infections in the lungs. For the treatment, a nanotherapeutic based inhalable antibiotic will be developed composed of a nanocarrier combined with an antimicrobial peptide. Based on the concentration of the drug in the lungs, level of toxicity side effects and the therapeutic efficacy of the nanoformulations used in pilot tests, the setup of the in vivo tests at Erasmus MC was fixed at the meeting.

PneumoNP’s consortium

PneumoNP’s consortium at its meeting in June 2017 in PathoFinder’s facilities

A visit to PathoFinder’s facilities rounded up the meeting. PathoFinder contributes to PneumoNP by improving the usage of antibiotics with the development of a diagnostic kit. The kit allows to identify antibiotic resistant strains of bacteria from a unique sample.

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Right before its end, PneumoNP is happy to announce its 2nd workshop. It will take place within the scope of the Molecular Imaging Workshop (MIW2017) organised by PneumoNP partner CIC biomaGUNE on November 20-23, 2017 in San Sebastian, Spain. The MIW2017 offers the opportunity to discuss molecular imaging applications to neurosciences and oncology. PneumoNP will take part with a half-day workshop on November 23, 2017. Several partners from the project will present their work in PneumoNP in relation to imaging.

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Meeting in Maastricht

PneumoNP: Exciting 6-month race ahead

With only six months to go before its end, the PneumoNP consortium gathered once more for their penultimate progress meeting ...
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Meet us at EuroNanoForum 2017

Iraida Loinaz, coordinator of the PneunoNP project, attends the EuroNanoForum 2017 conference. EuroNanoForum 2017 is an international event that focus ...
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Confront antibiotic resistance with a better diagnostic system

To slow down the rise of non-curable infections, a Dutch company developed a diagnostic kit to identify strains of antibiotic-resistant ...
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Confront antibiotic resistance with a better diagnostic system

To slow down the rise of non-curable infections, a Dutch company developed a diagnostic kit to identify strains of antibiotic-resistant bacteria.

medic-563425_960_720

The World Health Organization (WHO) warns citizens for several years now: many antibiotics are becoming useless to heal bacterial infections. Indeed, bacteria develop new defence mechanisms to resist the action of antibiotics. By accurate detection of these resistance mechanisms, prescription of useless antibiotics can be avoided. Instead, an appropriate antibiotic treatment can be prescribed to cure the patient.

A precise diagnosis contributes also to avoid the spread of resistant bacteria and the rise of new resistance mechanisms. Supposing all infections were treated with personalized antibiotic treatments, bacteria would have less room to evolve or to spread.

To tackle these challenges, the Dutch company PathoFinder strives to provide an on-time delivery and dependable diagnostic system. The kit will allows to identifying antibiotic resistant strains of bacteria from a unique sample. This new kit addresses the need of hospitals, where time and precision are valuable.

@PathoFinder, 2017

@PathoFinder, 2017

The kit, a PCR multiplex, can identify over 25 of the most important resistance gene families, namely carbapenemases, extended-spectrum beta-lactamases (ESBL), plasmid-mediated cephalosporinases (pAmpC) and plasmid-mediated colistin resistance genes.

PathoFinder, accredited of the ISO 13485, benefits from a long experience in medical devices’ design. This time, the team innovates with a multiplex that runs on standard laboratory equipments. About 3 years and a half were needed for the multiplex to be conceived. Later in 2017, the multiplex will enter clinical validation. It will need a few more official certifications before entering the market.

The company PathoFinder was supported by a European consortium of academic and private research groups. Indeed, the Dutch company participates to the PneumoNP project. The rapid development of the multiplex would not be possible without the contribution of their partners. Together they engage against the rise of antibiotic resistance. In this framework, PathoFinder contributes by improving usage of antibiotics with the development of the diagnostic kit.

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Meeting in Maastricht

PneumoNP: Exciting 6-month race ahead

With only six months to go before its end, the PneumoNP consortium gathered once more for their penultimate progress meeting ...
Read More
ENF2017_logo_web-red

Meet us at EuroNanoForum 2017

Iraida Loinaz, coordinator of the PneunoNP project, attends the EuroNanoForum 2017 conference. EuroNanoForum 2017 is an international event that focus ...
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Confront antibiotic resistance with a better diagnostic system

To slow down the rise of non-curable infections, a Dutch company developed a diagnostic kit to identify strains of antibiotic-resistant ...
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New publication: Into the killing activity of an antimicrobial peptide against antibiotic-resistant K. pneumoniae

Investigations into the killing activity of an antimicrobial peptide active against extensively antibiotic-resistant K. pneumoniae and P. aeruginosa

Abstracts

SET-M33 is a multimeric antimicrobial peptide active against Gram-negative bacteria in vitro and in vivo. Insights into its killing mechanism could elucidate correlations with selectivity.

Grpahical abstract of the publication: Investigations into the killing activity of an antimicrobial peptide active against extensively antibiotic-resistant K. pneumoniae and P. aeruginosa

SET-M33 showed concentration-dependent bactericidal activity against colistin-susceptible and resistant isolates of P. aeruginosa and K. pneumoniae. Scanning and transmission microscopy studies showed that SET-M33 generated cell blisters, blebs, membrane stacks and deep craters in K. pneumoniae and P. aeruginosa cells. NMR analysis and CD spectra in the presence of sodium dodecyl sulfate micelles showed a transition from an unstructured state to a stable α-helix, driving the peptide to arrange itself on the surface of micelles.

SET-M33 kills Gram-negative bacteria after an initial interaction with bacterial LPS. The molecule becomes then embedded in the outer membrane surface, thereby impairing cell function. This activity of SET-M33, in contrast to other similar antimicrobial peptides such as colistin, does not generate resistant mutants after 24 h of exposure, non-specific interactions or toxicity against eukaryotic cell membranes, suggesting that SET-M33 is a promising new option for the treatment of Gram-negative antibiotic-resistant infections.

Authors

Hessel van der Weide, Jlenia Brunetti, Alessandro Pini, Luisa Bracci, Chiara Ambrosini, Pietro Lupetti, Eugenio Paccagnini, Mariangela Gentile, Andrea Bernini, Neri Niccolai, Denise Vermeulen-de Jongh, Irma A.J.M. Bakker-Woudenberg, Wil H.F. Goessens, John P. Hays, Chiara Falciani

Sources

H. van der Weide et al. Investigations into the killing activity of an antimicrobial peptide active against extensively antibiotic-resistant K. pneumoniae and P. aeruginosa. Biochimica et Biophysica Acta (BBA) – Biomembranes, 2017. DOI: 10.1016/j.bbamem.2017.06.001.

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Meeting in Maastricht

PneumoNP: Exciting 6-month race ahead

With only six months to go before its end, the PneumoNP consortium gathered once more for their penultimate progress meeting ...
Read More
ENF2017_logo_web-red

Meet us at EuroNanoForum 2017

Iraida Loinaz, coordinator of the PneunoNP project, attends the EuroNanoForum 2017 conference. EuroNanoForum 2017 is an international event that focus ...
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medic-563425_960_720

Confront antibiotic resistance with a better diagnostic system

To slow down the rise of non-curable infections, a Dutch company developed a diagnostic kit to identify strains of antibiotic-resistant ...
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Call for abstracts for the Molecular Imaging Workshop 2017

The second edition of the Molecular Imaging Workshop 2017 (MIW2017) will be held from 20th to 23rd November 2017 in San Sebastian, Spain. Abstract submission is open until the 31st August 2017.

MIW 2017

Academic and industrial researchers are welcome to join the workshop. For instance an industrial forum is organized to exchange ideas and network. People can also submit abstracts to participate to the poster session.

Organized by CIC biomaGUNE, the workshop will cover topics related to molecular imaging. The MIW2017 is the opportunity to discuss molecular imaging applications to neurosciences and oncology. Do not miss the sessions dedicated to cardiovascular application, infection tracking and pneumology.

The PneumoNP project will also attend the event. Attendees will be updated of the latest results of the project.

Several invited speakers are already announced. Jesús Ruíz Cabello from the Complutense University of Madrid, Spain, will give a lecture on the “characterization of metabolic reprogramming in pulmonary hypertension”. Jason Holland will come from Zurich to discuss “PET radiotracers for imaging oncogenic signaling pathways”.
The full list of invited speakers is available on the MIW2017 website.

You can already submit your abstract for the MIW2017 and so until the 31st August 2017. All abstracts must be related to one of the following categories:

  • Oncology
  • Cardiology
  • Neurosciences
  • Infectious diseases and metabolism
  • Imaging technology, methodology and data analysis
  • Imaging probes
  • Pulmonology and respiratory

Changes in the application are accepted until the submission deadline. So, do not wait and submit your abstract on the MIW2017 website.

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Follow the PneumoNP team from event to event
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Meet us at EuroNanoForum 2017

Iraida Loinaz, coordinator of the PneunoNP project, attends the EuroNanoForum 2017 conference. EuroNanoForum 2017 is an international event that focus ...
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Molecular Imaging Workshop 2017

Call for abstracts for the Molecular Imaging Workshop 2017

The second edition of the Molecular Imaging Workshop 2017 (MIW2017) will be held from 20th to 23rd November 2017 in ...
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Meet us at ECCMID 2017

PneumoNP partners will attend ECCMID 2017 in Vienna, Austria, from 22-25th April 2017. ECCMID is a major event for experts ...
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The P.R.I.T.® lung model to test nanoparticle-based drugs

The German technology P.R.I.T.® with its air-liquid interface imitates lung behaviour. It is used for the first time to test a nanoparticle-based drug designed for inhalation.

Many studies require scientists to investigate effects of inhaled substances in lungs. One can think of studies related to smoking behaviors or urban pollution effects. Such studies are also needed for some drug development processes.  For example, the PneumoNP project develops a drug made for inhalation. Toxicity is tested also by investigating lung reactions under drug exposure.

There are several ways to forecast reaction of lungs to a substance without exposing humans. For example, animal models are used for clinical trials. Of course, ethical considerations encourage alternative methods to limit such in vivo tests. The Fraunhofer ITEM Institute in Hannover, Germany, developed an “in vitro model of lungs”. In 2017 and for the first time, this system, called P.R.I.T.®, will be used for testing nanoparticle-based drugs.

The P.R.I.T.® system belongs to the family of air-liquid interface setups. Basically, lung cells are placed on a membrane at the interface between the inhaled atmosphere and the culture medium that acts as blood input. These samples are exposed to a controlled test atmosphere containing the drug. Many parameters can be specifically defined like the composition of the air, the flow or even pressure. The great advantage of this technique is the almost-accurate replication of real-life lungs.

P.R.I.T.® air-liquid interface system principle and setup for the PneumoNP project

P.R.I.T.® air-liquid interface system principle and setup for the PneumoNP project

For the PneumoNP project, a nebulizer has been connected to the P.R.I.T.® system to test a drug made for inhalation. Scientists place human cells in the exposure unit and inject the nebulized drug in the air flow. The study aims to check the toxicity of the therapeutic formulation. Scientists are currently focussing on effects of the drug on lung cells and their genes. Using the P.R.I.T.® technology to test a nanoparticle-based drug is a premiere.

The Fraunhofer ITEM Institute is currently leading the study in their laboratory based in Hannover. First results will be publicly released by the end of the year. Beside the PneumoNP study, they use the P.R.I.T.® system within other projects for testing aerosols, particles and volatile organic compounds (VOCs).

 

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Read more PneumoNP news

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PneumoNP: Exciting 6-month race ahead

With only six months to go before its end, the PneumoNP consortium gathered once more for their penultimate progress meeting ...
Read More
ENF2017_logo_web-red

Meet us at EuroNanoForum 2017

Iraida Loinaz, coordinator of the PneunoNP project, attends the EuroNanoForum 2017 conference. EuroNanoForum 2017 is an international event that focus ...
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Confront antibiotic resistance with a better diagnostic system

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Review of 2016 before entering the last year of PneumoNP

Successful 2nd PneumoNP Review Meeting

Just as the new year has begun, the PneumoNP consortium came together in Brussels on January 16-17, 2017 for a combined 2-day Progress/Review Meeting.

The last three years in PneumoNP passed quickly with plenty of work already done towards developing a new method for the treatment of Klebsiella pneumoniae caused infections. The 4-year project is now entering its final phase in 2017. Therefore, the partners gathered together in Brussels for their 6th Progress Meeting which was dedicated to the progress made in the last six months but had a special focus on what the project needs to do in the next 11.5 months to bring the project to a successful end. This especially concerns the tests with different types of nanocarriers combined with Antimicrobial Peptides (AMPs) to obtain a novel effective inhalable antimicrobial nanosystem. The consortium got into fruitful discussions on the final steps to be implemented towards this goal.

“Great cooperation in working together”

On the second day, the consortium met Dr. Heico Frima, their EC Project Officer, and Dr. María Blanco Prieto as reviewer for their 2nd Review Meeting.

PneumoNP consortium

PneumoNP consortium at its meeting in January 2017

The coordinator and Work Package leaders presented the work done in 2015 and 2016 giving the Dr. Frima and Dr. Blanco Prieto the opportunity to assess the project’s progress and raise questions. Overall, the project’s progress and especially the interaction of the partners were evaluated positively. In this regard, Prof. Iseult Lynch, External Advisory Board member of PneumoNP, who joined the consortium for the Progress as well as the Review Meeting said: “This is a really engaged project. There is great cooperation in working together and solving problems together.” The consortium will endeavor to keep up this spirit for the final year.

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Read more PneumoNP news

Meeting in Maastricht

PneumoNP: Exciting 6-month race ahead

With only six months to go before its end, the PneumoNP consortium gathered once more for their penultimate progress meeting ...
Read More
ENF2017_logo_web-red

Meet us at EuroNanoForum 2017

Iraida Loinaz, coordinator of the PneunoNP project, attends the EuroNanoForum 2017 conference. EuroNanoForum 2017 is an international event that focus ...
Read More
medic-563425_960_720

Confront antibiotic resistance with a better diagnostic system

To slow down the rise of non-curable infections, a Dutch company developed a diagnostic kit to identify strains of antibiotic-resistant ...
Read More

Imaging data reveals nanomedicines in lungs

An experiment carried out in Spain shows the distribution of an inhaled nanomedicine in rat lungs.

The PneumoNP project aims at developing new inhaled nanotherapeutic formulations to combat lung infection. The novel drug is comprised of an antibiotic carried by a nanoparticle. For this project, Spanish researchers from CIC BiomaGUNE track the location of the therapeutic particles in rat airways.

The use of nanoparticles in formulations is anticipated to lengthen the residence time of the drug in lungs. Indeed, it is expected to slow down and control the release of the active molecules. This prevents rapid metabolism and fast clearance. So, the therapeutic effects are expected to increase. Besides, the delivery by inhalation contributes to diminish undesired toxicological and off-target side effects. The results obtained in imaging experiments are essential to establish the appropriate dosage to be used in therapeutic experiments with infected animals and to predict therapeutic efficacy.

PET image

Positron emission tomography image showing the regional distribution of aerosolized nanocarrier-antibiotic formulation in rat lung.

The researchers have developed labeling methods to incorporate different radionuclides to the nanocarrier and the antibiotic. Thanks to the different physical properties of the radionuclides, they visualize the spatiotemporal distribution of the nanocarrier and the antibiotic separately. To achieve that they also used complementary in vivo imaging modalities.

From imaging experiments, relevant information can be determined quantitatively by using only few experimental animals and extremely refined procedures. The percentage of administered dose that reaches the lungs is important to assess the efficacy of the aerosol delivery method. The researcher looks also for the regional distribution of the antibiotic and the nanocarrier within the lungs. With the spatiotemporal imaging, they evaluated the residence time of the active drug and the nanocarrier in the lungs.

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Action of a M33 peptide on the membrane of a gram-negative bacteria

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The antimicrobial peptide M33 may be the long-sought substitute to treat difficult lung infections, like multi-drug resistant pneumonia. In 2013, ...
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In vivo antibacterial activity of SET-M33L peptide in skin infection. Example of images of five animals at day 2.

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European Antibiotic Awareness Day 2016

Each year, European Antibiotic Awareness Day‘s campaigns encourage the prudent use of antibiotics on 18 November. Prudent use means only using antibiotics when needed. One should follow the prescribed dose, dosage intervals and duration of the treatment.

EAAD - European Antibiotic Resistance Awareness Day

Antibiotic-resistant bacteria have become an everyday occurrence and problem across Europe. Antibiotic resistance is the ability of bacteria to resist antimicrobial treatments. The excessive use of antibiotic contributes to the emergence of resistance. If we continue to consume antibiotics at the current rate, we may face a post-antibiotic era. If so, common bacterial infections such as pneumonia could be a death sentence.

In June 2016, the European Commission published a report on antimicrobial resistance awareness. Only a third of Europeans got information related to the correct use of antibiotics. Here is one of many reasons why we need more than ever an international awareness day.

Explaining the urge of new antibiotic is part of the project PneumoNP. Like every year on 18 November, the team disseminates content to European citizens. Stay informed on Twitter with us at @PneumoNP or with #EAAD.

Who measures the spread of antibiotic resistance?

In Europe, EARS-Net monitors antimicrobial resistance by a network of national surveillance systems. Since January 1999, laboratories have collected antimicrobial resistance data on more than 400,000 invasive isolates. EARS-Net performs surveillance of antimicrobial susceptibility of several bacterial pathogens including Klebsiella pneumoniae. The results are available from an interactive database. It provides information on the occurrence and spread of antimicrobial resistance in Europe.

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Read a summary of EAAD on social media


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Meeting in Maastricht

PneumoNP: Exciting 6-month race ahead

With only six months to go before its end, the PneumoNP consortium gathered once more for their penultimate progress meeting ...
Read More
ENF2017_logo_web-red

Meet us at EuroNanoForum 2017

Iraida Loinaz, coordinator of the PneunoNP project, attends the EuroNanoForum 2017 conference. EuroNanoForum 2017 is an international event that focus ...
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medic-563425_960_720

Confront antibiotic resistance with a better diagnostic system

To slow down the rise of non-curable infections, a Dutch company developed a diagnostic kit to identify strains of antibiotic-resistant ...
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A step forward towards therapeutic aerosols

A delivery device for a breathable drug has been prototyped to test a new drug formulation. It aims to fight respiratory tract infections.

To cure infections located in lungs, you can deliver antibiotic through the blood vessels or directly via the airways. Despite the many advantages of pulmonary delivery, few nebulization systems are designed.

The PneumoNP project develops an antibiotic formulation acting against drug resistant pneumonia. As it aimed for inhaled therapy, an aerosol system was chosen to deliver it. The Spanish company Ingeniatrics Technologías S.L. is in charge of prototyping the nebulizer device.

The Flow Blurring® nebulizer (©Ingeniatrics Technologías S.L.)

Picture 1: The Flow Blurring® nebulizer (©Ingeniatrics Technologías S.L.)

Setting up a nebulizer requires more than a random combination of compressed air and liquid. Indeed, the output needs to fulfill many conditions to be efficient.  Amongst others, the mist has to be breathable. So, droplets should be smaller than 3 μm to reach each corner of the lung. Achieving this result was especially challenging as the drug formulation contained large molecules.

Ingeniatrics used its technology called Flow Blurring® to produce the aerosol prototype. The Flow Blurring® relies on an atomisation technique that creates an ultra-fine mist from liquid; besides, it requires less energy compared to collision nebulizers. The microfluidic system produces turbulent mixing between a compressed air and the liquid drug. It yields droplets that are smaller than the output pipe. The system is versatile including, not only the proper fluid delivery accessories, but also the possibility to use mist chambers in combination with the Flow Blurring® technology.

illustration-scientifique-aerosol-v01-01

Picture 2: The Flow Blurring® technology adapted to drug delivery

As of today, the prototype is already in function. In the Dutch Erasmus Medical Center and in the Spanish CIC Biomagune laboratories, rats have been accustomed to the prototype setup. Now, researchers can look at the healing time of the rats when they inhale the drug. Initially designed for these in-vivo tests on rodents, the aerosol prototype has also been adapted to in-vitro investigations. In particular, researchers of the German Fraunhofer ITEM expose human epithelial lung cells to the therapeutic mist. They measure cytotoxicity and efficiency indices with this setup.

The aerosol delivery prototype will benefit from these users’ feedbacks for further refinement of the system. If the aerosol system is promising enough, it may become an industrial medical device for human or animal use.

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Learn more on Ingeniatrics’ activities

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PneumoNP: Exciting 6-month race ahead

With only six months to go before its end, the PneumoNP consortium gathered once more for their penultimate progress meeting ...
Read More
ENF2017_logo_web-red

Meet us at EuroNanoForum 2017

Iraida Loinaz, coordinator of the PneunoNP project, attends the EuroNanoForum 2017 conference. EuroNanoForum 2017 is an international event that focus ...
Read More
medic-563425_960_720

Confront antibiotic resistance with a better diagnostic system

To slow down the rise of non-curable infections, a Dutch company developed a diagnostic kit to identify strains of antibiotic-resistant ...
Read More

M33, the new option to fight severe pneumonia

The antimicrobial peptide M33 may be the long-sought substitute to treat difficult lung infections, like multi-drug resistant pneumonia.

In 2013, the European Respiratory Society predicted 3 millions cases of pneumonia in Europe every year[1]. The standard treatment for pneumonia is an intravenous administration of a combination of drugs. This leads to the development of antibiotic resistance in the population. Gradually, doctors are running out of solutions to cure patients. An Italian company suggests a new option: the M33 peptide.

Few years ago, the Italian company SetLance SRL decided to investigate the M33 peptide. The antimicrobial peptide is an optimized version of an artificial peptide sequence selected for its efficacy and stability. So far, it showed encouraging in-vitro results against multidrug-resistant Gram-negative bacteria, including Klebsiella Pneumoniae. With the support of EU funding to the PneumoNP project, SetLance SRL had the opportunity to develop a new formulation of M33 that enhances its antimicrobial activity.

Action of a M33 peptide on the membrane of a gram-negative bacteria

Fig. Action of a M33 peptide on the membrane of a gram-negative bacteria

 

The new formulation of M33 fights Gram-negative bacteria in three steps. First of all, the M33 binds with the lipopolysaccharides (LPS) on the outer membrane of bacteria. Then, the molecule forms a helix and finally disrupts the membrane provoking cytoplasm leaking. The peptide enabled up to 80% of mice to survive Pseudomonas Aeruginosa-based lung infections. Beyond these encouraging results, toxicity to the new M33 formulation seems to be much lower than antimicrobial peptides currently used in clinical practice like colistin[2].

Lately, SetLance scaled-up the synthesis route and is now able to produce several hundred milligrams per batch. The molecule is robust enough for industrial production. We may expect this drug to go on clinical development and validation at the beginning of 2018.

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[1] http://www.erswhitebook.org/chapters/acute-lower-respiratory-infections/pneumonia/

[2] Ceccherini et al., Antimicrobial activity of levofloxacin-M33 peptide conjugation or combination, Chem Med Comm. 2016;
Brunetti et al., In vitro and in vivo efficacy, toxicity, bio-distribution and resistance selection of a novel antibacterial drug candidate. Scientific Reports 2016

 

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Read more articles on PneumoNP activities

Meeting in Maastricht

PneumoNP: Exciting 6-month race ahead

With only six months to go before its end, the PneumoNP consortium gathered once more for their penultimate progress meeting ...
Read More
ENF2017_logo_web-red

Meet us at EuroNanoForum 2017

Iraida Loinaz, coordinator of the PneunoNP project, attends the EuroNanoForum 2017 conference. EuroNanoForum 2017 is an international event that focus ...
Read More
medic-563425_960_720

Confront antibiotic resistance with a better diagnostic system

To slow down the rise of non-curable infections, a Dutch company developed a diagnostic kit to identify strains of antibiotic-resistant ...
Read More