REVENCAP · Reversible Encapsulation
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2007-11-01 → 2008-12-31
- EU contribution
- €159,613
- Participants
- 1
- Scheme
- EIF
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - RevEncap (Reversible Encapsulation)
This project was the first step towards a reversible drugs encapsulation approach, whereby stable capsules were assembled by dynamic combinatorial chemistry (DCC) based on disulfide or hydrazone exchange. Our aim was to develop an original and promising drug delivery method to assemble specific capsules that would release their guest molecules, i.e. drugs, under the influence of a physiologically relevant trigger. The first step was to make mixtures of building blocks to generate different cage-like structures under equilibrium, held together by reversible covalent bounds such as disulfide or hydrazone bonds (dynamic combinatorial libraries). The available building blocks were very limited. Therefore, I synthesised new trithiol building blocks to produce a capsular structure as well as new building blocks based on hydrazone reversible covalent chemistry. Such building blocks required diverse functionalities e.g. aromatic or hydrophobic surfaces for guest recognition and water solubilising moieties. The combination of all these functionalities made the building blocks syntheses a real challenge. I also explored the use of the different obtained building blocks in order to produce with success a capsular structure in solution. Some of them led to the formation of capsules, which was an important achievement. Then I studied the introduction of a guest molecule into these building blocks mixtures that could lead to the stabilisation and amplification of a selective capsule that could accommodate this guest. No amplification was observed for the capsules based on disulfide exchange. These studies were still in progress, by the time of the project completion, in the host research group for the capsules formation based on hydrazone exchange.
Data: CORDIS, © European Union
Project objective
Drug delivery is the major hurdle to success of therapeutic treatments. A large number of potential drugs with high intrinsic activities fall by the wayside during the development because they have unfavourable physicochemical properties.The aim of this proposal is to develop a general strategy for the encapsulation of guest molecules inside container molecules. Current encapsulation strategies make use of- strong covalent bonds to form the molecular container under kinetic control, which results in essentially irreversible imprisonment of the guest; or- weak non-covalent interactions to assemble the capsules under thermodynamic control, leading to relatively labile products.Neither of these strategies is suitable for drug delivery. We will develop a new strategy towards encapsulation using thermodynamically controlled synthesis to assemble capsules that are held together by covalent bonds that are stable under ordinary conditions but that will release their guest under the influence of a physiologically relevant trigger.Capsules will be assembled by linking relatively simple building blocks together through disulfide bonds. We will prepare equilibrium mixtures (dynamic combinatorial libraries) of potential capsules under conditions of reversible disulfide bond formation. Introduction of a guest molecule into these mixtures should lead to the stabilisation of those capsules that can accommodate this guest.The concentration of the best capsules will increase, which should enable their identification. Once the structure of the selected capsules has been elucidated the same reversible chemistry can be used for thermodynamically-controlled capsule synthesis.Then, the conditions required for the release of the guest from the resulting capsules will be established in model systems that mimic a cellular environment. This approach may be developed for future use in drug targeting or other applications requiring controlled release of chemical substance.
Original text from CORDIS.
Participants
- University of Cambridge · CambridgeCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union