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ANTI-TB

Antibiotics nanocarrier for therapeutic inhalation against tuberculosis

 

Tuberculosis is worldwide the most relevant bacterial infectious disease in humans with around 10 million new cases in 2017. Its agent, Mycobacterium tuberculosis, tops the WHO list of the deadliest infectious diseases, which killed 1,6 million people in 2017. The pathogen hides in host scavenger cells encapsulated in inflammatory foci, the granulomas, in the infected tissue, primarily in the lung. Antibiotic treatment is required to be given for at least 6 months but is often accompanied by significant adverse effects, which can lead to premature termination of the therapy. Thereby, the occurrence of antibiotic-resistant strains is promoted further hampering successful therapy.

The "ANTI-TB – antibiotics nanocarrier for therapeutic inhalation against tuberculosis" consortium explores a nanomedical approach to better target the infectious hideout of tuberculosis agent thereby enhancing local but lowering systemic antibiotic levels. We hope this approach will help to limit future development of antibiotic resistance. Our nanocarriers are combined with novel anti-tuberculosis drugs to form antibiotic-nanocarriers. For targeting, nanocarrier surfaces are modified to be specifically recognized by infected cells for optimal transport to the pathogen’s intracellular niche. Most effective antibiotic-nanocarriers will be further developed for inhalation therapy to make application easier for the patients.

Our strategy aims to increase local drug concentration in infectious sites within lungs to shorten duration of therapy, reduce adverse effects and consequently, improve patient compliance.

 

Period:
2017 - 2020
Funding:
up to 3 Million Euro
Number of work Packages:
Consortium with a total of 6 Grant Recipients

 

News

 

 

MOOC Tuberculosis - Free online course

Free online course MOOC Tuberculosis, which will start on September 07, 2021. Free registration is open from June 14 to October 30, 2021.

The rich and multidisciplinary content of this MOOC is aimed at anyone who wants to dive into the fascinating science about Tuberculosis: its epidemiological and diagnostic data, the evolution of mycobacteria and Mycobacterium tuberculosis genome, the immunology of tuberculosis and host-pathogen interactions, the anti-tuberculosis agents currently in use and the antibiotic resistance, the development of new vaccine candidates and promising treatments against this disease and much more.

For more information, please visit the MOOC Tuberculosis website www.fun-mooc.fr/fr/cours/tuberculosis/

 


 

ANTI-TB Consortium Meeting in Saarbrucken

anti tb meeting saarbruecken

 The final meeting in Saarbrucken in June 2021 had to be moved to an online format again due to the COVID 19 pandemic. Therefore, the research results of the different subprojects were presented and discussed via video conference. Dr. Thomas Hesterkamp, DZIF, who supported the consortium as an advisor during the funding period 2017-2021 participated as a guest and gave supportive and helpful advice for further directions.

Screenshot of the participants from the partner Institutes Research Center Borstel (ANTI-TB Coordinator: Prof. Dr. Ulrich E. Schaible), Helmholtz Institute for Pharmaceutical Research Saarland, Fraunhofer ITEM, Karlsruhe Institute of Technology, and University of Vienna.

 

 


 

Press release March 18, 2021

World Tuberculosis Day 2021: Trend of decreasing tuberculosis case numbers in Germany must become a permanent development

Susanne Glasmacher Press and Public Relations

Robert Koch Institute Berlin

Germany is well placed to achieve the World Health Organization's tuberculosis elimination targets. Tuberculosis is an infectious disease that is generally easy to treat, but which nevertheless affects about 10 million people worldwide every year and kills about 1.4 million. On the occasion of World Tuberculosis Day on March 24, the Epidemiological Bulletin of the RKI addresses the topic of tuberculosis with a series of articles in its current issue 11/2021 [..]

idw-online.de

 


 

Press Release November 11, 2020

DGP: German Central Committee for the Control of Tuberculosis celebrates 125th birthday

Successful infection control in Germany

Association of the Scientific Medical Societies e.V.

The German Central Committee for the Control of Tuberculosis e. V. (DZK) celebrates 125th birthday [..]

idw-online.de

 


 

ANTI-TB Consortium Meeting

The planned semi-annual consortium meetings - in Potsdam in May, in Saarbrucken in September 2020 - were cancelled due to the COVID 19 pandemic. The research results of the subprojects were therefore presented and discussed via video conference.

 


 

Press Release July 8, 2020

Internatuional recommendations for non-tuberculous mycobacteria

Karola Neubert Press and Public Relations

German Center for Infection Research

After 13 years, a panel of experts has issued new recommendations for the treatment of patients with non-tuberculous mycobacteria (NTM). The need for current recommendations [..]

idw-online.de

 


 

Press release March 12, 2020

World Tuberculosis Day 2020 - Progress and targets

Susanne Glasmacher Press and Public Relations

Robert Koch Institute Berlin

The year 2020 marks the beginning of a decade that will be decisive for the elimination of tuberculosis," said Prof. Dr. Lothar H. Wieler, President of the Robert Koch Institute, on World Tuberculosis Day on 24 March [..]

idw-online.de

 


 

Press Release December 11, 2019

Tuberculosis: New drug substance BTZ-043 is being tested on patients for the first time

Philipp Kressirer Communications and Media

Clinic of the University of Munich

The Tropical Institute at the Hospital of the Ludwig Maximilian University (LMU) in Munich is currently conducting a clinical study led by Professor Michael Hoelscher. Since mid-November, the first tuberculosis patients in Cape Town, South Africa, have been treated with the new drug substance BTZ-043 for the first time. The study is carried out within the PanACEA consortium in cooperation with the TASK Applied Science Clinical Research Centre, the University of Cape Town Lung Institute (UCTLI) and the Radboud University Medical Center [..]

 idw-online.de

 


 

ANTI-TB Consortium Meeting in Karlsruhe

Foto: Gebäude 30.45, C. Feldmann, privat

The BMFT-funded ANTI-TB consortium meets alternatingly at the partner institutes twice a year - usually in spring and autumn.

From May 5th to 6th 2019, the third consortium meeting took place at the Institute of Inorganic Chemistry (Project partner: Claus Feldmann) at the Karlsruhe Institute of Technology (KIT). During the meeting, all partners presented their recent results to be discussed by the all participants.  On the second day, all partners discussed the next steps and upcoming tasks for the second half of the funding period (2017-2020).

 

 


 

Reading tip: Nanoparticles - Use in medicine

Nanoparticles can provide valuable services in many areas of medicine: whether in diagnostics, e.g. in the early detection of various types of cancer, or in therapy, through the development of so-called nanocarriers, which can transport drugs specifically to the sources of disease. Helmholtz Center Munich, in cooperation with the German Centre for Lung Research (DZL), has now published an overview article on the current state of research and the future of medical nanoparticles on its Lung Information Service portal: www.lungeninformationsdienst.de

 


 

Congratulations: Scientist from the ANTI-TB team receives “Winfried Möller Research Award”

ANTI TB Team gewinnt Winfried Möller Research Award02.06.2019. Benedikt Huck received the "Winfried Möller Research Award" at the 22nd Congress of the International Society for Aerosols in Medicine (ISAM) in Montreux / Switzerland, 2019. Benedict Huck is a PhD student in the ANTI-TB team "Drug Transport" in Claus-Michael Lehr’s group at the Helmholtz Institute for Pharmaceutical Research (HIPS) in Saarbrücken.

This award is given in memory of Professor Winfried Möller - who died in 2017 - by his family, friends and colleagues under the patronage of the AtemWeg Foundation. The €500 prize is awarded to young scientists for successful research in Prof. Möllers' field on aerosol particles and their interactions in the lung.

This biennial international conference brings together over more than 200 aerosol scientists, pharmacists, clinical doctors and regulatory authorities from all over the world.

 

 

 


 

Press release March 13, 2019

Tuberculosis - eliminate one of the oldest disases of mankind!

Susanne Glasmacher Press and Public Relations

Robert Koch Institute Berlin

The number of tuberculosis cases in Germany in 2018 was similar to 2017, but an annual decrease of 10 percent would be necessary to achieve the World Health Organization's goal of eliminating tuberculosis by 2050 [..]

idw-online.de

 


 


 

ANTI-TB Consortium Meeting in Hannover

Photo: K. Schwarz, privatThe BMFT-funded ANTI-TB consortium meets alternatingly at the partner institutes twice a year - usually in spring and autumn.

The first meeting took place from February 28 to March 01, 2018 in Halle at MLU Halle-Wittenberg as part of the CRS Local Chapter Meeting "Locally controlled delivery and more" March 01-02 which was organized by partner Prof. Dr. Lea Ann Dailey (Vice President CRS Local Chapter Germany).

On October 4 - 5, 2018, the project partners met at the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) in Hanover. The coordinator, Professor Ulrich E. Schaible (Research Centre Borstel), welcomed 20 participants, including Dr. Lisette Leonhardt, VDI/VDE-IT, and the external consultant of the network, Dr. Thomas Hesterkamp, Helmholtz Centre for Infection Research/TPMO, as guests, to the second meeting. The project partners reported on the progress of the individual subprojects. During the meeting, the results and the next steps were presented and discussed.

On the following day, all participants had the opportunity to visit the Fraunhofer ITEM (partner: Dr.-Ing. Katharina Schwarz, center of picture) and learn about the different projects at ITEM.

 

 

 

 

 

 

 


Press release October 24, 2017

With small particles against tuberculosis: BMBF supports nanomedical research project to fight against therapy-resistant pathogens

Over the next three years, the ANTI-TB research consortium will receive 2.8 million Euros of funding from the German Federal Ministry of Education and Research (BMBF). The aim of the project is use nanocarriers to improve therapies of antibiotic resistant tuberculosis. The project partners include the Borstel Research Centre, the Leibniz Institute for Medicine and Biosciences (FZB), the Karlsruhe Institute of Technology (KIT), the Fraunhofer Institute for Toxicology and Experimental Medicine Hanover (ITEM), the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), the Martin Luther University Halle-Wittenberg (MLU-HW) as well as the biopharmaceutical company Rodos Biotarget GmbH (RBT). The Borstel Research Centre is the coordinator of this innovative research network. Rodos Biotarget is responsible for the commercialization of the research and development results.

With 2.2 billion infected people worldwide, tuberculosis is the most important bacterial infection in humans. According to the WHO, 10.4 million people worldwide contracted tuberculosis in 2015 alone and 1.8 million died as a result of the infection. The fight against tuberculosis is hampered by the increased occurrence of therapy-resistant strains of the pathogenic agent, which is further accelerated by therapy drop outs. "Patients with multi-drug resistant or extensively drug resistant tuberculosis must take medication for up to 24 months - with sometimes severe adverse effects. With our new therapeutic approach, we aim to target specifically the infectious foci in order to enhance local drug concentrations, shorten duration of therapy and minimize systemic adverse effects. Thereby, we hope to increase the willingness of patients to stick to the therapy to the very end and reduce drop-out rates to 50%" said Prof. Ulrich E. Schaible, Director of the Program Area Infections at the Borstel Research Centre and coordinator of ANTI-TB.

In order to improve tuberculosis therapy and limit further development of resistant strains of the tuberculosis agent, ANTI-TB follows a nanomedical approach by constructing nanocarriers of only a few nanometers in diameter and a modified surface carrying address molecules for infected cells. These nanocarriers are loaded with novel antibiotics should specifically target infectious sites in the lung. "The aim of our joint project is to develop antibiotic nanocarriers ready for clinical testing. The most effective variants will be designed for an aerosol or powder-based inhalation therapy," explains Professor Schaible. "Through inhalation, we hope to increase antibiotic concentrations in the infected lungs to minimize length of therapy and to reduce the burden of adverse effects for the patients.”

In the field of medical imaging and tumor therapy, nanomaterials are intensively studied, and some are already in clinical use. Nanocarriers as transport systems for antibiotics have so far been less developed. ANTI-TB starts exactly at this point. The interdisciplinary cooperation between chemists, pharmacists and microbiologists within this consortium will lead to the development of a new therapeutic concept that could also become applicable to other diseases in the future. While KIT and Rodos Biotarget are designing novel nanocarriers, ITEM and HIPS are developing inhalable formulations, the Pharmaceutical Institute of the University of Halle is carrying out toxicological studies. The FZB, with its expertise in tuberculosis research, uses appropriate infection models to investigate the efficacy of the new therapeutics against the tuberculosis agent. As an enterprise, Rodos Biotarget will finally generate the most effective formulations according to international quality standards ready to be marketed.

Against the background of increasing resistance of bacterial pathogens to antibiotics, the Federal Ministry of Education and Research (BMBF) established the program "Promotion of Diagnostics and Novel Therapies for the Treatment of Bacterial Infections" in 2016. Thereby, the BMBF hopes to advance the development of new diagnostics for the targeted use of antibiotics as well as the development of novel therapies for the treatment of bacterial infections in human medicine. The ANTI-TB research project was approved by the BMBF at the end of September and will start on October 1st, 2017.

 

Work Packages

 

Bio-sharing and efficacy testing of new antibiotics nanocarrier 

Funding Code: 16GW0164K
Total Funding: 920.886 EUR
Period: 2017 - 2020
Project Prof. Dr. Ulrich E. Schaible
Adress: Borstel Leibniz Lung Centre Research Centre
Parkallee 1-40
23845 Bo
rstel

 

Synthesis of inorganic antibiotic-loaded nanocontainer

Funding Code: 16GW0165
Total Funding: 473.184 EUR
Period: 2017 - 2020
Project: Prof. Dr. Claus Feldmann
Adress: Karlsruhe Institute of Technology (KIT)
Engesserstr. 15
76131 Karlsruhe

  

Inhalative application 

Funding Code: 16GW0166
Total Funding: 289.995 EUR
Period: 2017 - 2020
Project: Dr. Katharina Schwarz
Adress: Fraunhofer Institute of Toxicology and Experimental Medicine (ITEM)
Nikolai Fuchs Str. 1
30625 Hannover

 

Optimizing interactions with the fluid film of the lungs and
developing powder formulation to inhalate antibiotic nanocarrier s
ystems 

Funding Code: 16GW0167
Total Funding: 453.525 EUR
Period: 2017 - 2020
Project: Prof. Dr. Claus-Michael Lehr
Adress: Helmholtz Center for Infection Research GmbH
University Campus E8 1
66123 Saarbrücken

 

In-Vitro and In-Vivo toxicology of antibiotics nanocarrier

Funding Code: 16GW0168
Total Funding: 293.814 EUR
Period: 2017 - 2020
Project: Prof. Dr. Lea Ann Dailey
Adress: Martin Luther University Halle-Wittenberg
Wolfgang-Langenbeck-Str. 4
06120 Halle

 

Synthesis of antibiotic-loaded nanocarrier (NC)

Funding Code: 16GW0169
Total Funding: 405.215 EUR
Period: 2017 - 2020
Project: Dr. Marcus Furch, Dr. Robert Gieseler von der Crone
Adress: Rodos Biotarget GmbH
Feodor Lynen-Str. 31
30625 Hannover

 

 

 

Project Partner

 

                                      Priority Research Area Infections, Cellular Microbiology, Bioanalytical Chemistry

 

                                                 Institute for Inorganic Chemistry (AOC), AK Feldmann

 

                                                Division of Chemical Safety and Toxicology, Department of Aerosol Technology and Biophysics

 

          Research Area Antiinfectives, Department of Drug Delivery

 

                       Institute of Pharmaceutical Technology and Biopharmacy, Research Group Biopharmacy

 

                                                 Biopharmaceutical company

   

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Save the Date

 

BioBarriers 2021 | September 7-8 2021 | Saarbrücken, Germany

From innovation to intervention EMBO-Workshop Tuberkulose 2021 | September 13-17 2021 | Paris, France

52nd Union World Conference on Lung Health | A virtual event | 19-22 October 2021

 
 

Publications

        

  • Thiyagarajan D, Huck B, Nothdurft B, Koch M, Rudolph D, Rutschmann M, Feldmann C, Hozsa C, Furch M, Besecke KFW, Gieseler RK, Loretz B, Lehr C-M. Spray‑dried lactose‑leucine microparticles for pulmonary delivery of antimycobacterial nanopharmaceuticals. Drug Delivery and Translational Research 2021 May 25. doi.org/10.1007/s13346-021-01011-7; https://link.springer.com/article/10.1007/s13346-021-01011-7
  • Rudolph D, Redinger N, Schaible UE, Feldmann C. Transport of Lipophilic Anti‐Tuberculosis Drug Benzothiazon‐043 in Ca3(PO4)2 Nanocontainers. ChemNanoMat 10.1002/cnma.202000421, doi.org/10.1002/cnma.202000421
  • Global tuberculosis report 2020
  • Patel A, Redinger N, Richter A, Woods A, Neumann PR, Keegan G, Childerhouse N, Imming P, Schaible UE, Forbes B, Dailey LA. In vitro and in vivo antitubercular activity of benzothiazinone-loaded human serum albumin nanocarriers designed for inhalation. J Control Release 2020 Aug 19. Epub 2020 Aug 19, doi.org/10.1016/j.jconrel.2020.08.022
  • Global tuberculosis report 2019
  • Huck BC, Hartwig O, Biehl A, Schwarzkopf K, Wagner C, Loretz B, Murgia X, Lehr CM. Macro- and microrheological properties of mucus surrogates in comparison to native intestinal and pulmonary mucus. Biomacromolecules. 2019 Aug 16, doi: 10.1021/acs.biomac.9b00780. www.ncbi.nlm.nih.gov
  • Rein V, Meschkov A, Hagens K, Redinger N, Schepers U, Mehlhorn H, Schaible UE, Feldmann, C. Zirconyl Hydrogenphosphate Nanocontainers for Flexible Transport and Release of Lipophilic Cytostatics, Insecticides, and Antibiotics. Adv. Funct. Mater. 2019, 29: 1900543 doi.org
  • Amaral EP, Costa DL, Namasivayam S, Riteau N, Kamenyeva O, Mittereder L, Mayer-Barber KD, Andrade BB, Sher A. A major role for ferroptosis in Mycobacterium tuberculosis–induced cell death and tissue necrosis. J Exp Med. 2019 Mar 4; 216 (3):556-570 doi: 10.1084/jem.20181776. Epub 2019 Feb 20
  • Global tuberculosis report 2018
  • Kletting S, Barthold S, Repnik U, Griffiths G, Loretz B, Schneider-Daum N, de Souza Carvalho-Wodarz C, Lehr C-M. Co-culture of human alveolar epithelial (hAELVi) and macrophage (THP-1) cell lines. ALTEX 2018; 35 (2): 211-222. Open Access; www.altex.org
  • Murgia X, Loretz B, Hartwig O, Hittinger M, Lehr C-M. The role of mucus on drug transport and its potential to affect therapeutic outcomes. Advanced Drug Delivery Reviews 2018, 124: 82-97
  • Kuehn A, Kletting S, De Souza Carvalho-Wodarz C, Repnik U, Griffiths G, Fischer U, Meese E, Huwer H, Wirth D, May T, Schneider-Daum N, Lehr, C-M. Human alveolar epithelial cells expressing tight junctions to model the air-blood barrier. Altex 2016; 33 (3): 251-260. Open Access www.altex.org
  • Frenz T, Grabski E, Durán V, Hozsa C, Stępczyńska A, Furch M, Gieseler RK, Kalinke U. Antigen presenting cell-selective drug delivery by glycan-decorated nanocarriers. Eur J Pharm Biopharm 2015 Sep ;95(Pt A):13-7. doi: 10.1016/j.ejpb.2015.02.008. Epub 2015 Feb 19
  • Leidinger P, Treptow J, Hagens K, Eich J, Zehethofer N, Schwudke D, Oehlmann W, Lünsdorf H, Goldmann O, Schaible UE, Dittmar, KEJ, Feldmann C. Isoniazid@Fe2O3 Nanocontainers and Their Antibacterial Effect on Tuberculosis Mycobacteria. Angew Chem Int Ed 2015; 54:12597 onlinelibrary.wiley.com
  • Raesch SS, Tenzer S, Storck W, Rurainski A, Selzer D, Ruge CA, Perez-Gil J, Schaefer UF, Lehr, C-M. Proteomic and Lipidomic Analysis of Nanoparticle Corona upon Contact with Lung Surfactant Reveals Differences in Protein, but Not Lipid Composition. ACS Nano 2015, 9 (12): 11872-11885. pubs.acs.org
  • Griffiths G, Nyström B, Sable SB, Khuller GK. Nanobead-based interventions for the treatment and prevention of tuberculosis. Nature Rev Microbiol 2010;8:827 www.ncbi.nlm.nih.gov
  • Gieseler RK, Marquitan G., Hahn M. J., Perdon, L. A., Driesseny WHP, Sullivan SM, Scolaro MJ. DC-SIGN-Specific Liposomal Targeting and Selective Intracellular Compound Delivery to Human Myeloid Dendritic Cells: Implications for HIV Disease. Scand J Immunol. 2004; 59, 415–424