Project: Silicone hydrogel for Control of Resistant bacteria

Urinary catheters and other urological devices are used in enormous numbers worldwide. However, their use increases the patient’s risk of contracting a urinary tract infection. The overall aim of the present project is to solve this problem by adding a new delivery system for drugs that will prevent catheter related urinary tract infections._x000D__x000D_This project proposes to develop the new type of catheter by combining the advantages of silicone rubber with an antibacterial hydrogel network. This approach is unique because it is based on impregnated silicone instead of a coating or a “tea bag” solution which frequently results in a too rapid release profile for the drug, i.e. a burst release which is initially therapeutically relevant but then tapers to low level diffusion – with no therapeutic effect. The silicone hydrogel is flexible, tunable and can be modified to deliver drugs in a very controlled way for several months. _x000D__x000D_The key issues for this project are CONTROLLED release and LONG TERM release. For decades this has been the major challenges when functionalizing medical devices. Therefore, the approach adopted in this project is a paradigm shift for preventing infections and bacterial multi-drug resistance in a highly effective and unprecedented way. _x000D__x000D_The key component of the new technology is an innovative process developed by one of the project Ps (BioModics), whereby polymers are intercalated into silicone matrices using supercritical carbon dioxide (scCO2) to make an Inter Penetrating Network (IPN). By using this technique, the porosity of the silicone is increased which makes it possible to introduce drugs into the polymer network. Such a network will be able to COtain a surface coating for months. The resulting hybrid material will prevent infections and, equally important, prevent formation of resistant bacteria spreading along the catheter surfaces. _x000D__x000D_The rationale of the project is based on growing evidence showing that selection of bacteria primarily happens when large populations of bacteria are exposed to high doses of antibiotics. The proposed project will involve site-specific release of comparatively much lower amounts of drug to prevent effective bacterial adhesion and microcolony formation. Hence, biofilms never establish and the resistance-factories herein are prevented. In contrast, present device-associated infections are treated at the point where mature biofilms are already established, which has massive consequences for the patient, the environment and for formation of resistant bacteria. _x000D__x000D_The project will explore the interplay between polymer, silicone and drug to gain a better understanding of polymer-drug interactions and release mechanism. This will enable a rational development of IPNs containing different drugs and polymers for specific purposes and routes of administration. Suitable in vitro release models will be developed, to verify that the drug is released under specific circumstances at the proper time and place. In addition, the relationship between loading technology, choice of antimicrobials, release profiles and clinical requirements will be optimised. _x000D__x000D_The silicone hydrogel IPN will solve a range of problems associated with current delivery technologies. There is a strong societal need for drug delivery technologies that enable non-invasive delivery with a release rate that can be modified to fit the requirement of a specific treatment. Such technologies will result in fewer side effects, better primary effects and easier drug administration and thus will benefit the patient._x000D__x000D_The proposed consortium, consisting of BioModics (Denmark, SME), DTI (Denmark, Research institute), and LEMI (France, SME), presents a unique collection of expertise extremely well suited to the proposed project. _x000D_BioModics has developed the silicone hydrogel IPN device and brings expertise in the development of this material. BioModics will lead and coordinate the project and be responsible for specific tasks within material development, integration of silicone matrix and antibacterial hydrogel, system design, imaging and testing._x000D_DTI is a research institute with a long track record of development projects within biomedical polymer technology. DTI will be responsible for material and synthesis development and optimization, up-scaling requirements and characterization of mechanical and physico-chemical properties of the materials._x000D__x000D_LEMI has the capability to provide an expert evaluation in compliance with regulatory standards and to assist in research and development, taking into account recent advances in technology. LEMI will be responsible for the assessment of the efficacy of the new device by in vitro testing and toxicological evaluation.

Acronym CoRe (Reference Number: 5489)
Duration 01/09/2010 - 31/08/2013
Project Topic The project objective is to develop the first fully integrated silicone hydrogel drug delivery devices. By fulfilling this objective large unmet market demands for easy controlled and safe long time prevention of biofilms and bacterial resistance will be met.
Project Results
(after finalisation)
Proof-of-concept that drugs can be stored and released from a hybrid silicone-hydrogel material._x000D_Proof-of-concept that active drugs can be linked/combined with silicone rubber and induce mucoadhesiveness.
Network Eurostars
Call Eurostars Cut-Off 4

Project partner

Number Name Role Country
3 BioModics Coordinator Denmark
3 Laboratoire d'Evaluation des Matériels Implantables Partner France
3 Danish Technological Institute Partner Denmark