H2020Индивидуална стипендия2020–2022

BacDrug · Bacterial membrane vesicles a novel delivery system for the treatment of multi-drug resistant Gram-negative bacterial infections.

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2020-03-01 → 2022-02-28
Финансиране от ЕС: 212 934 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Многослойни частици, заредени с антибиотици, се тестват за борба с устойчиви бактерии като MRSA. Тези системи освобождават лекарството само при наличие на бактериални токсини, което подобрява ефекта на терапията и намалява страничните ефекти върху организма.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Bacterial membrane vesicles a novel delivery system for the treatment of multi-drug resistant Gram-negative bacterial infections.

One of the milestones in medicine was the discovery of antibiotics which prevent/treat bacterial infections and by this saved millions of lives. Conventional systemic antibiotic therapy is often limited by instability of the drug, cytotoxicity and negative effects on the patient’s microbiota. Additionally the global spread of antimicrobial resistant (AMR) bacteria, such as Pseudomonas aeruginosa and Staphylococcus aureus, combined with a dearth of R&D of novel antibiotics are a significant public health challenge and alternative treatment strategies are urgently needed. The overall goal of this Marie Skłodowaska-Curie Fellowship was to develop a drug delivery platform to overcome the limitation of conventional antibiotic therapy and tackle AMR. In this project multilayered particles (based on capsosomes) were engineered with a high carry capacity for lipid-based vesicles. This vesicles can be loaded with single drugs or offer the benefit of delivering drug combinations. In this project lipid-based vesicles mimicking human cells were used to implement a bacterial toxin triggered release mechanism. As a proof-of-concept single (vancomycin) or dual loaded (vancomycin and antimicrobial peptide) capsosomes were developed and their activity towards the multi-drug resistant methicillin-resistant Staphylococcus aureus (MRSA) was tested. The capsosomes engineered in this project released their cargo only in the presence of toxin producing MRSA and exhibited excellent antibacterial activity in vitro and in vivo. Additionally, the delivery of dual drugs resulted in an enhanced killing effect even at lower antibiotic concentrations. Overall, the results provided in this project have made significant progress towards a drug delivery system for multi-drug resistant bacteria with the potential to tackle one of the biggest health care crises of our day. The success of this ambitious project was highly dependent on the placement within the world-renowned Stevens Group and the close collaboration with the Edwards Group at Imperial College London. The interdisciplinary expertise of these groups was the ideal host for this project and critical for the highly promising outcomes of this work. As a result of this fellowship an ongoing close collaboration between the Stevens Group and the Edwards Group was established which is the steppingstone to further develop this drug delivery system for clinical applications and tailor it towards other critical pathogens.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Bacterial infections are a significant public health challenge and a major cause of human mortality globally. Antibiotics are indispensable for the treatment and prevention of infections caused by bacteria. However, global spread of drug-resistant bacteria, coupled with a dearth of new antibiotics in development has led to an alarming shortage of effective drugs. Gram-negative bacteria, in particular, protect themselves against antibiotics with a highly selective outer membrane. The high burden of diseases caused by Gram-negative bacteria, combined with their frequent multi-drug resistance has placed them as world´s highest-priority pathogens by the World Health Organization. Consequently, there is an urgent need for novel therapeutic approaches that combat Gram-negative bacterial pathogens. The goal of ""BacDrug"" is to use lipid-based bacterial membrane vesicles (BMVs) produced by non-pathogenic Lactococcus lactis as delivery system. BMVs have great potential as nanocarriers to by-pass the outer membrane and deliver their toxic payload to kill drug-resistant Gram-negative pathogens. A range of strategies will be used to load BMVs with cargo, including genetic engineering of L. lactis as well as chemical treatments. This Fellowship will harness expertise and techniques across microbiology, molecular biology, nanotechnology and drug design to deliver a successful outcome. The collaborative, truly interdisciplinary, cross faculty setting within the groups of Prof Molly Stevens (materials and bioengineering) and Dr Andrew Edwards (molecular microbiology) at ICL combines world-class expertise and provides an environment to maximise the success of this Fellowship, both in terms of the delivering the project and the training opportunities provided. Moreover, this innovative, alternative strategy to tackle drug-resistant Gram-negative bacterial infections has a high translational potential, which will be exploited via the clinical and translational research clinics at ICL.""

Оригинален текст от CORDIS (на английски).

Участници

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE · LondonКоординаторОбединеното кралство