CD Amélioration de la biodisponibilité orale du cannabidiol via l'absorption lymphatique pour action cérébrale : impact de la formulation lipidique

Encadrement

4. The scientific leaders; PhD student's host research units 4.1. Human scope This thesis project, co-directed by Pr Isabelle Lartaud and Dr Marianne Parent from CITHEFOR and Pr Socrates Egito from UFRN, will include the participation of other CITHEFOR staff, notably Arnaud Pallotta (assistant professor, analytical chemistry specialist), Thomas Chaigneau (research engineer, analytical chemistry specialist) and Alexandra Kleinclauss (assistant engineer, cell experiments) and UFRN staff with the contribution of the collaborators of Prof. Egito, notably the ones from the Brain Institute of Research, Laboratory of Quality Control and the NUPLAN, a Pharmaceutical Facility of the UFRN in which products in industrial scale are produced for future clinical trials and development of new pharmaceutical products. Drawing on the skills of UFRN and CITHEFOR, with strong local partnerships, the project has a major innovative component in the development of formulations for CBD therapeutic use. Through the Capes-Cofecub program, links have already been forged between the two research units (CITHEFOR and UFRN) for several years now. In particular, Pr Egito has visited France several times, and Dr Parent went to Brazil last winter. Moreover, CITHEFOR is currently welcoming several Brazilian students. A PhD co-supervision is a unique opportunity to pursue and consolidate the collaboration between the two teams. 4.2. Integration and support in the Research Units' strategy CITHEFOR's entire organization is based on a Quality Management System (QMS). This system aims to meet the requirements of ISO 9001 version 2015 and is based on the general principles and recommendations for the Quality approach in research of standard NF X 50-553 of July 2014. The aim is to enable all staff, students and stakeholders to have a complete view of the organization of CITHEFOR team and to integrate seamlessly into it. The Quality Manual, and the documentation derived from it, apply to all the activities of the CITHEFOR team, as well as to all staff, whether permanent or temporary (visiting professors, contract staff, PhD students, trainees, etc.). The Quality Manual is supplemented by procedures and instructions setting out the operational provisions relating to Quality. All newcomers to our organization meet (1) the team manager, who introduces them to our research policy and QMS objectives, and (2) their direct supervisor, who explains how the UR operates. At this stage, training needs for the use of the various equipment (pH meter, automatic pipettes, spectrophotometers and high-performance liquid chromatography, etc.) are assessed and planned. Trainers are designated by the supervisor, based on technical documents and instructions relating to the equipment. (3) The Quality coordinator introduces the newcomer to the team, and gives him or her the Welcome Booklet, which contains the internal regulations and describes the operation of the QMS, outlining the procedures and instructions to be applied. The newcomer certifies that he or she is aware of the health and safety measures in place, and undertakes to comply with the Université de Lorraine's IT Charter and to apply the QMS. The Thesis Charter is then co-signed by the direct supervisor and the doctoral student before the other signatures are obtained. This thesis charter commits the supervisors and the doctoral student to a doctoral program based on defined rules. A visit to the team's premises is organized to enable the newcomer to familiarize himself with his working environment and to meet the research team's staff. In Brazil the applicant will have all the support for produce the new carriers (dosage forms) for CBD, and will be able to deal with a plethora of techniques. The Laboratory of Dispersed Systems (LaSiD), coordinated by Prof. Sócrates Egito, comprises two laboratories, two study and research rooms, and a faculty office, totaling 200 m². Additionally, LaSiD is equipped with various instruments that will support the execution of this proposal, including a Malvern Zetasizer, a Netzsch STA system (TG-DSC), a spectrophotometer, high-precision analytical balances (0.00001 g), an ultrasound probe, a water purification system consisting of a distiller, deionizer, and reverse osmosis system, an ultrasound bath, an Eppendorf centrifuge, Ultra-Turrax agitation systems for different volumes, magnetic stirrers with temperature control, overhead stirrers, rotary evaporators, pH meters for organic and aqueous solutions, a conductometer, a turbidimeter, and other essential equipment. Beyond its in-house infrastructure, LaSiD maintains partnerships with other laboratories at UFRN and collaborating institutions in Brazil (UFRJ, UFMS, and UNESP), which provide the necessary technical support for additional analyses. As a result, the laboratory has unrestricted access to laminar flow hoods for in vitro experiments with human cell cultures, animal facilities, and specialized teams for in vivo studies. Researchers also have access to advanced equipment such as tensiometers, rheometers, ZetaPlus, scanning, transmission, and atomic force electron microscopy, circular dichroism, infrared spectroscopy, GC-FID, and HPLC MS-NMR, among others. Additionally, all researchers have access to auditoriums and amphitheaters, which are suitable for hosting annual scientific discussion meetings. The following paragraphs provide additional information on the support provided. 5. PhD student supervision 5.1. Resources deployed 5.1.1. For the understanding, appropriation and potential development of the project Within UR 3452, various scientific events take place periodically (twice a month), in the form of a presentation of a scientific article related to the subject by one of the team's PhD students, or a presentation of his or her results. This provides an opportunity to confront the literature and receive constructive criticism from UR staff, so as to consolidate the student's progress, either through a bibliographical study, or through additional experimental work. The same activities are offered in LaSiD. Additionally, as part of the formation of the applicant, Masters's student and Young Researchers' students will be guided by the applicant throughout their projects. In this way, the ability to advise students will be developed in the applicant. In addition, the BioSE Doctoral School rules provide for the organization of annual Thesis Follow-up Committees. The supervisors, the doctoral student and two colleagues (one internal to the Université de Lorraine, the other external) take part in these meetings. 5.1.2. for the appropriation of methods and tools CITHEFOR's QMS includes all the team's equipment in a Quality perimeter (arrival on our premises, life sheet, qualification follow-up, etc.) (from the automatic pipette to the most sophisticated equipment, such as dynamic light scattering devices dedicated to nanoparticle size measurement). What's more, the new protocols and methodologies most widely used in the team are drafted by the PhD student, then checked by a second student or a permanent member of staff, and finally validated by another permanent member of staff. Within the LaSiD the applicant will have the opportunity to work with several apparatus after his/her formation by the person responsible of the equipment. He/She will also be able to work with new procedures of a laboratory in which all the equipment has been properly qualified by experts and follow the SOP (Standard Operation Procedures) tailored by each different analysis. 5.1.3. For material, intellectual and personal well-being The PhD student will initially be supported by the research unit's grant, pending the submission of an ANR research project in October 2025 and an Université de Lorraine interdisciplinary project in March 2026. On the LASID side we will try to add funds, if necessary, for a perfect stay in Brazil. The applicant will be placed in a safe environment surrounded by several colleagues who will give all the technical, economical and emotional support to do his/her research work with a great peace of mind. The PhD student will also have easy access to CITHEFOR's computer and bibliographic resources via the team's common server and the Université de Lorraine website, enabling him/her to rapidly acquire a culture of the themes addressed. Doctoral students will be strongly encouraged by their supervisors to join the BioSE Doctoral School's “AD'UL Team” and the ORION scientific clubs (e.g. “What Health”) to facilitate their integration and foster scientific and human exchanges between young researchers. The same environment will be offered at LASID. The research team of Prof. Egito has weekly meeting for discuss science and, after the meeting, we have happy hours for strength the relationship among its members. To support the doctorate and avoid any possible conflict between supervisors and doctoral students, thesis committees will be organized with a time for meetings between invited members and the doctoral student alone. Finally, experiments will be carried out during the day, according to the laboratory's opening hours, with periodic rest periods/holidays. 5.1.4. For the preparation of the defense The BioSE Doctoral School organizes annual meetings of the thesis monitoring committee. The last meeting must authorize the PhD defense, based on the following factors: duration, number of publications and rank of the PhD student in the order of authors, participation in congresses, etc. A written report by colleagues on the thesis monitoring committee is sent to the Doctoral School for this purpose. At the same time, the scientific activities scheduled by UR 3452 and LASID include oral presentations by doctoral students, in particular before their thesis defense, to prepare them for this event by asking questions put forward by the various team members. 5.1.5. Career prospects Through the doctoral training, doctoral student will have consolidated her/his knowledge of pharmaceutical technology, analytical chemistry, in vitro evaluation and pharmacokinetics applied to the development and evaluation of an oral formulation for CBD. Depending on her/his wishes, doctoral student will be guided to help build a curriculum vitae in line with her/his career plans. There are two main ways in which trained doctoral students can enter the professional world: (i) Thanks to the skills acquired, newly-qualified PhD will be able to enter the professional world in a variety of companies, particularly those in the pharmaceutical sector (drugs or medical devices) as young research manager. (ii) The PhD will also have the opportunity to work on contract research contracts (such as post-doctorate or temporary teaching and research assistantship), and subsequently join a company as a senior researcher, or public scientific and technological establishments as a research associate or lecturer. After registering for a PhD, the student must follow the rules of the ED BioSE doctoral school to authorize the defense. A number of these rules are designed to facilitate the professional integration of doctoral students. For example, students must obtain 30 credits before they can defend their doctorate. Some of these credits are earned through participation in scientific conferences, days or congresses, while others are earned through professional integration training courses such as “Ma thèse en 180 secondes”, the Doctoriales de Lorraine or the Doctoriales Européennes, participation in training courses for Doctorants Contractuels Chargés d'Enseignements, or participation in career guidance fairs (training catalogs are available on the doctoral school website). Her/his work will also be submitted for prizes (Faculty of Pharmacy, Université de Lorraine, Académie Nationale de Pharmacie, etc.). The doctoral student may be offered a contract teaching position to gain teaching experience (tutorials and practical work) in disciplines related to his or her research (Pharmaceutical Technology and Biopharmacy). Co-supervision of interns (Master 1, Master 2, introductory research internship, research internship) will be managed by the doctoral student. Doctoral students will be asked to keep their ADUM profile up to date (skills acquired, publications accepted, communications given, etc.) to make them more visible for job offers. In conclusion, all these activities will enable him/her to consolidate his/her profile as a researcher so as to enter the world of work under the most favorable conditions. From our side, at the LaSiD, we are sure that participating in a joint PhD program between France and Brazil offers an exceptional opportunity for the candidate to develop not only advanced technical expertise but also invaluable human and cultural skills. Through this international collaboration, the student will gain access to cutting-edge research facilities, work alongside leading experts, and immerse his/herself in a diverse academic environment that fosters innovation and scientific excellence. Beyond the technical and scientific benefits, this experience will provide a unique opportunity for cultural exchange, allowing the student to engage with peers from different nationalities, perspectives, and research backgrounds. This interaction will enhance his/her adaptability, communication, and problem-solving skills—critical attributes for a successful researcher in today's globalized world. This dual formation will be truly unique, shaping the candidate into a highly skilled researcher or professor capable of training future generations. By fostering knowledge transfer and international collaboration, this initiative will create a positive cycle of scientific advancement, ensuring a lasting impact on academia and innovation.