Friday 22 September 2017

Faculté de Pharmacie
3, rue du Professeur Laguesse
BP83 - 59006 - Lille Cedex
Tél. : +33 (0)3 20 96 40 40
Fax : +33 (0)3 20 95 90 09
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Coordinator

INSERM U1008, University of Lille 2, Lille (Prof. Dr. Juergen Siepmann)

Duration of the project

4 years

INI - Innovative Inner Ear Treatments

 

Nature of the project:
Project funded by the French Research Agency (Lien externe - Ouverture dans une nouvelle fenêtreANR) (2016-2020)

Summary of the project:
The aim of this project is to open up new horizons for innovative medical treatments of the cochlear of the inner ear. New therapeutic strategies will be developed for ear ailments, in particular hearing loss.

Despite the availability of highly potent drugs, which could be of great benefit for the patients, most treatments are nowadays not possible because the drug cannot reach its target site: the inner ear. This is due to the blood-cochlear barrier, which effectively hinders drug transport from the systemic circulation into the inner ear. Thus, upon administration via conventional routes (e.g. oral, i.m., i.v.) the drug does not reach its site of action. Direct injection into the inner ear presents an effective means to overcome the blood-cochlear barrier, but frequent administrations would be required due to drug elimination. This is not possible because of the risk of infections and the sensitivity of the very small fluid volume in the cochlear to fluctuations. Advanced drug delivery systems allowing for local and time-controlled drug release offer the potential to overcome these crucial hurdles. However, up to date most approaches in this domain show significant variability, since the residence times of the proposed systems at the administration site generally significantly vary in vivo, due to their more or less rapid elimination. This results in high uncertainty with respect to the drug amount reaching the inner ear and the time period during which the drug is delivered. This uncertainty leads to unreliable therapeutic efficacy and safety concerns for the patient.

The aim of this project is to overcome this fundamental bottleneck and to assure reliable local controlled drug delivery to the inner ear. Two types of advanced drug delivery systems will be developed:

  • bioadhesive, liposome-loaded gels, administered onto the round window membrane and releasing the drug during several hours, days or weeks, and
  • intracochlear implants, inserted directly into the inner ear and releasing the drug at the site of action during several months or years.

The two types of devices are complementary and can be expected to allow for a much more reproducible control of the drug concentrations at the site of action and, thus, improved therapeutic efficacy and treatment safety. The drug will be embedded within biocompatible polymeric matrices (optionally containing liposomes), which will prohibit instantaneous release upon administration and assure controlled drug release over pre-programmed time periods. Intratympanic gels and intracochlear implants loaded with different drugs will be prepared by polymer rehydration with liposome suspensions and injection molding, respectively. Their performance will be tested in vitro and in vivo (animals). Variation of the manufacturing processes and compositions of the systems will allow for the optimization of the resulting drug release kinetics. A thorough physical characterization of the implants and gels and mechanistically realistic mathematical modeling will allow for understanding how the devices work. Furthermore, the mechanical key properties of the systems will be monitored to assure convenient handling by the surgeon.

The expected results of this project include:

  • Prototypes (implants and gels) and know-how to prepare innovative drug delivery systems allowing to overcome the blood-cochlear barrier,
  • Knowledge of the key features of these new types of devices,
  • Possibility to allow for new therapeutic strategies to treat inner ear ailments, and
  • Comprehensive data bases on the in vitro and in vivo performance of the systems, serving as a starting point for clinical trials envisaged as follow-up studies.

As an industrial company specialized on high-tech intracochlear electrodes (commercializing drug-free implants) is part of the consortium, also the economic exploitation of the new findings is foreseen in the long run.

 





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