Description du sujet de thèse

Historically, pharmaceutical oral or topical dosage forms were limited to a restricted number of conventional forms, such as disk-like or spherical tablets, cylindrical capsules, rectangular patches, etc., with the active ingredient uniformly distributed in the excipient. In the past few decades, there appeared numerous new dosage architectures, which allow novel administration routes and/or allow targeted drug delivery, enabling better therapeutic action while reducing adverse effects.
In particular, elastomeric ring-shaped sustained release forms have attracted much attention, due to their efficiency for the drug administration close to the target organ. Thus, Bimatofrost® containing silicon ring which sits under the eyelids and releases the drug for up to six months was developed for the treatment of glaucoma. A ring-like device made of a polymer gel that can deliver drugs to the stomach over the course of a week was developed by researchers from MIT. On the other hand, customized dosage forms, which release drugs or multidrugs with the rates and in the amounts accommodated to the needs of individual patients or groups of patients, became today the mainstream of the research at the interface of pharmacology and materials science.
The objective of the thesis consists in the development of the novel ring-shaped pharmaceutical forms for personalized gastroretentive drug administration.
The project pursues two major objectives, which arise from the state of the art and our expertise in the field [1,2]:
1) The development of rolled-up ring-shaped gastro-retentive drug delivery systems (RS-GRDDS) for personalized drug release. Personalization of the release kinetics will be achieved via the design of the position of the drug reservoirs inside the rings.
2) In vitro and in vivo study of the release kinetics of model drugs from the RS-GRDDS with the use of an appropriate in vitro medium (Fasted state simulated Gastric Fluid) and of the animal models (pigs). The ring-shaped gastro-retentive drug delivery systems can release the drugs as foreseen and cannot be degraded before the total release of the drugs. Additionally, due to the fact that the RS-GRDDS have to stay in the stomach, a good correlation can be observed between the in vitro and in vivo releases.
The scientific and technical barriers to be lifted :
a) Despite promising preliminary results, the RS-GRDDS fabrication needs essential improvements, in order to make the device acceptable by the medical community. The rings need to be produced in a more automatic manner, in order to reduce the production cost and improve the reproducibility of the release kinetics.
b) The physico-chemical and mechanical characteristics of the rings need to be investigated in detail in course of the in vitro and in vivo experiments.
The project includes research in materials science and pharmaceutical studies, conducted jointly by the Institute of Materials Science of Mulhouse and the Faculty of Pharmacology of the University of Strasbourg.
The thesis is funded by a grant from the National Agency for Research. This is a full time position for 3 years. This project aims to develop a new gastro-retentive drug formulation for personalized medication delivery. We are studying the stability of these coated formulations, based on biopolymers such as gelatin, in physiological media mimicking gastric and intestinal fluids. The drug release rate will be modulated by its position within the formulation. Finally, these new formulations will be tested in vivo in an animal model.
Apart of publications in high-ranked journals, the doctoral student will have the opportunity to present his or her results and the national and international conferences.
Bibliographical references
[1] Q.-H. Tran, A. ur Rehman, T. Vandamme, V. Luchnikov, Rolled-up gastroretentive gelatin rings for controlled release of riboflavin and captopril, Int. J. Pharm. 680(2025), 125795 https://doi.org/10.1016/j.jddst.2024.105563
[2] J. Mzoughi, Q. H. Tran, G. Schrodj, T. Vandamme, V. Luchnikov, Rolled-up gastroretentive oral dosages for controlled release of riboflavin and propranolol, Journal of Drug Delivery Science and Technology, 95 (2024)105563, https://doi.org/10.1016/j.jddst.2024.105563
Activities :
The PhD student shall participate in the design of a small production line for the fabrication of the pharmaceutical forms with standard characteristics. He or she will study their physico-chemical properties of the forms (mechanical characteristics, stability in the model gastrointestinal fluids), and measure the drug release profiles in these model media. Next, the sudent will take part in the in vivo tests of the drug administration in collaboration with the national veterinary school of Maison-Alfort.

Contexte de travail

The selected PhD student (male/female) will join the Institute of Materials Science of Mulhouse (IS2M), a joint research unit of the CNRS and the University of Haute-Alsace (UHA) (UMR 7361). They will be affiliated with the doctoral school of the University of Haute-Alsace (ED 182).
This laboratory is a key player in the field of materials science and their applications in academia and industry, both regionally and nationally. For more information about IS2M, please visit the website: https://www.is2m.uha.fr/.
The student (male/female) will work under the supervision of Mr. Valeriy Luchnikov within the team Interfaces and Multidimensional Materials.
The Institute of Materials Science in Mulhouse is located on the Illberg campus of the University of Upper Alsace in a dynamic region bordering Germany and Switzerland: TGV train station and airport 40 minutes away.
Benefits include: mobility allowance and a fixed contribution towards transportation and health insurance costs, university cafeteria, continuing education, and supplemental health insurance.

Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.

Contraintes et risques

The ideal candidate is motivated, adaptable, and willing to integrate into a multidisciplinary team, and open to new ideas and concepts. Proven experience in experimental device design and engineering skills will be valued. Knowledge of pharmaceutical laboratory equipment and spectroscopic methods (UV-VIS, IR, Raman) is highly desirable.