Author Archives: Bénédicte Huchet

Antibiotic resistance: Hope may come from small biotech companies

Discover Adenium, a small biotech company from Denmark. It develops the molecule that may become the next generation of antibiotics.

Every antibiotic in use today is based on a discovery made more than 30 years ago”. This is a worriedly observation done by the Pew Trust Charity in 2016. Indeed, antibiotics become less and less efficient. And since the 80’s, no new mechanism to fight bacterial infections has been brought onto the market.

Major Classes of Antibiotics

Click to enlarge

Despite their investments and efforts, big pharma companies struggle to develop a new class of antibiotic drug. For the company supporting the initiative, developing a brand new drug is demanding. It requires to take risks, and enough flexibility to change plans with new approaches if needed. What if the solution comes from small biotech companies?

In the race against the rising antibiotic resistance, smaller research companies emerge. For instance, the Danish biotech company Adenium Biotech is committed to finding the next therapeutic mechanism. They explore the potential of a new group of antimicrobial peptides called Arenicin-3. Peptides of this group have the advantage to attack bacteria membranes in a novel way.

Arenicin3 3D model

AA139 peptide – ©AdeniumBiotech

In particular, one molecule of the Arenicin-3 group is very promising: the AA139 peptide. Indeed, it is not toxic to human tissues and seems to have high bacteria-killing activity, including bacteria that are resistant to currently available antibiotics. For these reasons, it was judged by Adenium as a good candidate for drug development.

In 2014, the Danish company joined the EU-funded PneumoNP project as the AA139 peptide was at an early preclinical stage. The European project was a good opportunity for Adenium to test AA139 and compare the peptide to other promising molecules. Now, Adenium has GMP produced AA139 and is progressing toward clinical development.

Also, the PneumoNP project explored an interesting area for AA139. The project team loaded the peptide in a shell made of a nanoparticle and results showed that AA139 retained its antimicrobial activity after encapsulation. Results of the related studies should be published soon.

Currently, only a few non-traditional antibiotics are under clinical development. There are probiotics, antibodies, and vaccines. Antimicrobial peptides build hope for a new class of novel antibiotics. At the end, the innovation might come from small biotech companies like Adenium.

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Read more PneumoNP news

Major Classes of Antibiotics

Antibiotic resistance: Hope may come from small biotech companies

Discover Adenium, a small biotech company from Denmark. It develops the molecule that may become the next generation of antibiotics ...
Read More
Graphical abstract

New publication: Experimental methods for aerosol measurements in human airways

Experimental methods for flow and aerosol measurements in human airways and their replicas Abstract Recent developments in the prediction of ...
Read More
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

New publication: Experimental methods for aerosol measurements in human airways

Experimental methods for flow and aerosol measurements in human airways and their replicas

Abstract

Recent developments in the prediction of local aerosol deposition in human lungs are driven by the fast development of computational simulations. Although such simulations provide results in unbeatable resolution, significant differences among distinct methods of calculation emphasize the need for highly precise experimental data in order to specify boundary conditions and for validation purposes.

This paper reviews and critically evaluates available methods for the measurement of single and disperse two-phase flows for the study of respiratory airflow and deposition of inhaled particles, performed both in vivo and in replicas of airways. Limitations and possibilities associated with the experimental methods are discussed and aspects of the computational calculations that can be validated are indicated.

Graphical abstract

The review classifies the methods into following categories:

  1. point-wise and planar methods for velocimetry in the airways,
  2. classic methods for the measurement of the regional distribution of inhaled particles,
  3. standard medical imaging methods applicable to the measurement of the regional aerosol distribution and
  4. emerging and nonconventional methods.

All methods are described, applications in human airways studies are illustrated, and recommendations for the most useful applications of each method are given.

Authors

Frantisek Lizal, Jan Jedelsky, Kaye Morgan, Katrin Bauer, Jordi Llop, Unai Cossio, Stavros Kassinos, Sylvia Verbanck, Jesús Ruiz-Cabello, Arnoldo Santos, Edmund Koch, Christian Schnabel

Source

Lizal, F., Jedelsky, J., Morgan, K., Bauer, K., Llop, J., Cossio, U., … & Koch, E. (2017). Experimental methods for flow and aerosol measurements in human airways and their replicas. European Journal of Pharmaceutical Sciences.

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Read more PneumoNP news

Major Classes of Antibiotics

Antibiotic resistance: Hope may come from small biotech companies

Discover Adenium, a small biotech company from Denmark. It develops the molecule that may become the next generation of antibiotics ...
Read More
Graphical abstract

New publication: Experimental methods for aerosol measurements in human airways

Experimental methods for flow and aerosol measurements in human airways and their replicas Abstract Recent developments in the prediction of ...
Read More
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

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 on how nano and materials technologies can strengthen competitiveness across all European industries. The event takes place in Malta from 21th and 23th June 2017.

Nanotechnology is expected to gain importance in the near future in many industries. For example, nanomedicine could solve numerous healthcare challenges especially in the field of drug-delivery. However, from the pharmaceutical point of view, there is insufficient clinical data that allows the assessment of the role of nanotechnology in the potential of these products.

It is time to push those promising developments to the clinical stage. Iraida Loinaz’s talk will show real examples on how is possible to translate a lab scale protocol, into a robust GMP manufacturing process, and those key aspects to take into account to reduce the time of development.


Iraida Loinaz, coordinator of PneunoNP project, is the Health business development Manager of IK4-Cidetec. In the last years Dr. Loinaz’s group has been specialized in translational research. They are establishing a pilot plant operating under GMP for the production of nanopharmaceuticals.

“It is my first time attending EuroNanoForum,” Dr Loinaz said. “I really look forward to meeting main stakeholders in the field of nanotechnologies for health and share our experiences in the field.”

Find all the necessary information related to the event on: www.eccmid.org.

EuroNanoForum 2017 logo

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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 ...
Read More
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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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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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Read more PneumoNP news

Major Classes of Antibiotics

Antibiotic resistance: Hope may come from small biotech companies

Discover Adenium, a small biotech company from Denmark. It develops the molecule that may become the next generation of antibiotics ...
Read More
Graphical abstract

New publication: Experimental methods for aerosol measurements in human airways

Experimental methods for flow and aerosol measurements in human airways and their replicas Abstract Recent developments in the prediction of ...
Read More
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

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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Read more PneumoNP news

Major Classes of Antibiotics

Antibiotic resistance: Hope may come from small biotech companies

Discover Adenium, a small biotech company from Denmark. It develops the molecule that may become the next generation of antibiotics ...
Read More
Graphical abstract

New publication: Experimental methods for aerosol measurements in human airways

Experimental methods for flow and aerosol measurements in human airways and their replicas Abstract Recent developments in the prediction of ...
Read More
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

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
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
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 ...
Read More
7_ECCMID_Vienna 2017 picture-logo_480x310

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 ...
Read More

Meet us at ECCMID 2017

PneumoNP partners will attend ECCMID 2017 in Vienna, Austria, from 22-25th April 2017.

ECCMID2017

ECCMID is a major event for experts of infectious diseases and clinical microbiology. A wide range of these topics will be discussed during symposia and poster sessions.

Several PneumoNP partners attend ECCMID 2017. They will present and discuss the latest results of the PneumoNP projects.

PathoFinder will have a company booth. They will display next generation multiplex PCR diagnostics kits for infectious diseases. One is under development in the framework of the PneumoNP project.

On Sunday 23rd, Alessandro Pini, from the company SetLance, will give a presentation during the session: Host-pathogen interactions provide opportunities for novel therapy. The session takes place in hall H from 11:30 to 12:30. His presentation will covers “the peptide SET-M33 as novel agent to neutralize and remove LPS in patients with sepsis”.

Meet us also during the session: New drugs against Gram-negatives. The session takes place in hall K on Monday 24th from 09:00 to 11:00. Chiara Falciani, from the company SetLance, will give a presentation entitled “An antimicrobial peptide to face multidrug-resistance emergency: synergies and mechanism of action underpinning efficacy”.

Find all the necessary information related to the event on: www.eccmid.org. The full programme is available on the website ECCMIDLive.

__________________________________________________________________
Follow the PneumoNP team from event to event
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
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 ...
Read More
7_ECCMID_Vienna 2017 picture-logo_480x310

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 ...
Read More

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

Major Classes of Antibiotics

Antibiotic resistance: Hope may come from small biotech companies

Discover Adenium, a small biotech company from Denmark. It develops the molecule that may become the next generation of antibiotics ...
Read More
Graphical abstract

New publication: Experimental methods for aerosol measurements in human airways

Experimental methods for flow and aerosol measurements in human airways and their replicas Abstract Recent developments in the prediction of ...
Read More
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

New publication: Synthesis of Single–Chain Nanoparticles in Aqueous Media

Synthesis and Functionalization of Dextran–Based Single–Chain Nanoparticles in Aqueous Media

Abstracts

Water-dispersible dextran-based single-chain polymer nanoparticles (SCPNs) were prepared in aqueous media and mild conditions. Radiolabeling of the resulting biocompatible materials allowed the study of lung deposition of aqueous aerosols after intratracheal nebulization by means of single-photon emission computed tomography (SPECT), demonstrating their potential use as imaging contrast agents.

Authors

Raquel Gracia, Marco Marradi, Unai Cossío, Ana Belen Benito, Adrián Pérez-San Vicente, Vanessa Gómez-Vallejo, Hans J Grande, Jordi Llop and Iraida Loinaz

Sources

Gracia R et al. Synthesis and Functionalization of Dextran–Based Single–Chain Nanoparticles in Aqueous Media. J. Mater. Chem. B, 2017. DOI: 10.1039/C6TB02773C.

__________________________________________________________________

Read more PneumoNP news

Major Classes of Antibiotics

Antibiotic resistance: Hope may come from small biotech companies

Discover Adenium, a small biotech company from Denmark. It develops the molecule that may become the next generation of antibiotics ...
Read More
Graphical abstract

New publication: Experimental methods for aerosol measurements in human airways

Experimental methods for flow and aerosol measurements in human airways and their replicas Abstract Recent developments in the prediction of ...
Read More
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

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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illustration-scientifique-aerosol-v01-01

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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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Heal pulmonary infections with nanosystems

Fine nanosystems carrying Meropenem and antimicrobial peptides to fight pulmonary infections are ready for in vitro tests. Before 2016 starts, ...
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