CLIMB · Development of a Cavity Supported Lipid Membranes Biomimetic drug permeability models (CLIMB)
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2018-01-01 → 2019-12-31
- Финансиране от ЕС
- 175 866 €
- Участници
- 1
- Схема
- MSCA-IF-EF-ST
Линиите свързват координатора с партньорите.
Накратко на български
Изработват се изкуствени клетки от нанофотонни структури, за да се проследи как лекарствата преминават през клетъчната мембрана. Това помага за по-бързо и евтино предвиждане на ефективността на нови медикаменти при рак, вирусни инфекции и неврологични разстройства.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Development of a Cavity Supported Lipid Membranes Biomimetic drug permeability models (CLIMB)
Majority of therapeutic molecules must overcome membrane barrier before reaching their site of action. However, optimal delivery of drugs has always remained elusive in the pharmaceutical industry. This cannot be more true for diseases such as neurological disorders, cancers, and viral infections, which have affected millions globally, causing billion-dollar worth of productivity loss worldwide. Yet, delivery issues remain largely unresolved. In principle, one could increase the chance of Identifying a drug with both good delivery efficiency and the desired therapeutic efficacy by screening hundreds of thousands or more drug candidates. Unfortunately, such an endeavor is formidably uneconomical. The current project is to address this challenge – to devise a platform for the accurate prediction of drug’s membrane permeability in a high-throughput manner. To meet this vision, the main objective of the current project is to provide a proof-of-principle demonstration of how prudently designed nano-photonic structures can be made to mimic an actual cell in terms of drug uptake. While cell-based assay is conventionally used, it is laborious and expensive as biological cells needed to be cultured and kept in a sterilized condition. To this end, this project seeks to develop a novel platform bearing photonics-based ‘artificial cells’, for the study of drug plasma membrane interactions. The cells provide cell membrane analogues across which molecule binding, entry and diffusion dynamics can be monitored using multiple distinct analytical modalities including Electrochemsitry, Raman and Fluorescence Spectroscopy. The modalities can be combined and the methods selected depend on the characteristics of the drug. In conclusion, it is showed that the ‘artificial cells’ can display uptake behavior characteristic of real biological cells for representative libraries of drugs from different drug categories. More importantly, using a multi-modal approach, the current method is also able to reveal the underlying mechanism of drug-transport across the membrane, that was normally obscured in traditional cell-based assays. For more details on this project and related publications, please visit https://sites.google.com/dcu.ie/keyes-research-group/research.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Permeability Assay (PAMPA) have limited biorelavance and can often be poorly predictive of of drug permeation, particularly for charged species and for complex membranes such as the BBB and particularly of membrane toxicity which remain key issue leading to high attrition rate and low productivity in the pharmaceutical industry. The proposed fellowship programme aims to address these issues in a very novel way by developing lipid bilayers supported on cutting-edge Plasmonically-Directed Nano-Structured porous arrays. The substrates prepared via a range of fabrication methods, including 2-photon 3D-nanoprinting, will allow for investigation of drug-membrane interactions, and permeability through a unique and novel principle, whereby the arrival time of single or few weakly- or non-fluorescent molecules at plasmonic volume in the nano-/micro-cavity is monitored via enhanced spectroscopic technique. Angle dependent Raman microscopy will permit study independently of the drug-membrane interactions and plasmonic hot spot so both structural and permeation times can be meausered and these studies will be carried out in parallel with Elelctrochemcial impendence spectroscopy of membrane integrity. This approach will dramatically advance the state-of-the-art in membrane assay. In parallel it provide high quality research training to the MRSA fellow along with, supported by the host institution training programme a range of career promoting transferable skills acquired. Leading the fellow to a fully-independent academic position.
Оригинален текст от CORDIS (на английски).
Участници
- DUBLIN CITY UNIVERSITY · DublinКоординаторИрландия
Връзки
Данни: CORDIS, © Европейски съюз
