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ANR funded project

Innovation biomédicale (DS0404) 2014
Projet Imperio

In-situ forming implants for periodontitis treatment

Periodontitis is a highly prevalent, chronic inflammatory disease of the periodontium, leading to the destruction of the tooth supporting tissues and finally tooth loss. Microorganisms in the patients’ periodontal pockets produce molecules, which directly attack the host tissue, and/or cause an immune response leading to tissue destruction. Periodontitis is the main cause for tooth loss in adults: 47% of the US adults have mild, moderate or severe periodontitis (64% of the population > 65 years). The treatment of periodontitis is highly challenging, since drug partitioning into the periodontal pockets is not very pronounced and gingival fluid flow rapidly eliminates the drug from the site of action. Hence, using conventional administration routes, high systemic drug levels are required, while the drug concentration at the target site remains low. This leads to potentially severe side effects and low therapeutic efficacy, despite the availability of highly potent drugs able to act against the pathogenic flora and inflammation. These hurdles can be overcome using local controlled drug delivery systems: In this case, the drug is directly administered at the site of action and its release is controlled during prolonged periods of time. Different types of systems have been proposed; however most of them contain antibiotic drugs and exhibit insufficient adhesion to the walls of the periodontal pockets, combined with inappropriate mechanical properties. This leads to uncontrolled expulsion of at least parts of the systems during the treatment and, thus, unreliable drug exposure to the target site. The aim of this project is to overcome these severe bottlenecks and to develop innovative in-situ forming implants, which: (i) are easy to inject (as liquid formulations), (ii) readily spread within the patients’ pockets and adapt their geometry and size to the individuals’ needs, (iii) exhibit reliable residence times due to improved bioadhesion and adequate plasticity, and (iv) control the release of non-antibiotic drugs during optimized periods of time. The basic idea is to dissolve the drug (or a combination of drugs) together with a biodegradable matrix former in a common solvent. This liquid is administered using standard syringes into the patients’ pockets. Once in contact with aqueous body fluids, the solvent diffuses out of the system, causing the precipitation of the matrix former and drug entrapment. The latter is subsequently released in time-controlled manner at the target site. This leads to optimized therapeutic efficacy and reduced drug exposure to the rest of the human body, thus, minimized side effects. Due to the biodegradability of the in-situ formed implant, empty remnants do not need to be removed after drug exhaust. A highly interdisciplinary consortium encompassing pharmacists, dentists, microbiologists, immunologists, physicists, chemists etc., offers the whole range of innovation: from clinical expertise to advanced research, through technological development, up to cutting-edge evaluation in animal models. New types of in-situ forming implants will be prepared and thoroughly characterized in vitro as well as in vivo (periodontitis mouse model). For instance, MS imaging (MALDI) will allow getting deeper insight into the underlying mass transport mechanisms, drug release kinetics and pharmacodynamic efficacy of the systems, mapping for example the spatial distribution of the drug and inflammation markers in the animal tissue. The obtained comprehensive database on the performance and key features of the innovative drug delivery systems will serve as a basis for the conduction of clinical trials, which are envisaged as follow-up studies. With a French SME being part of the consortium, also the economic exploitation of the results is foreseen. Importantly, non-antibiotic drugs will be studied, thus, the project will contribute to the combat against the development of bacterial resistances.

Partners

INSERM U 1008 Controlled Drug Delivery Systems and Biomaterials

ImaBiotech ImaBiotech

INSERM U 995 Inflammation : mécanismes de régulation et interactions avec la nutrition et les candidoses

INSERM UMR 1109 Osteoarticular and Dental Regenerative Nanomedicine Laboratory

CNRS UMR 8207 Unité Matériaux et Transformations

ANR grant: 796 993 euros
Beginning and duration: octobre 2014 - 48 mois

 

ANR Programme: Innovation biomédicale (DS0404) 2014

Project ID: ANR-14-CE16-0025

Project coordinator:
Madame Florence SIEPMANN (Controlled Drug Delivery Systems and Biomaterials)

 

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The project coordinator is the author of this abstract and is therefore responsible for the content of the summary. The ANR disclaims all responsibility in connection with its content.