Phd Position

**JOB ENVIRONMENT**:

- Institut Mines-Télécom_ is the leading public group of engineering and management _Grandes Écoles_ in France. Consisting of eight public graduate _Grandes Écoles_ and two subsidiary graduate schools, _Institut Mines-Télécom_ leads and develops a rich ecosystem of partner schools, economic, academic and institutional partners, key players in education, research and economic development.

Mines Saint-Étienne, a graduate school of the _Institut Mines-Télécom_, is responsible for education, research, innovation, industrial transfer and scientific culture dissemination. With 2,500 students, 500 staff and a budget of €50m, it has 3 campuses dedicated to the industry of the future, health and well-being, and digital sovereignty and microelectronics. It is ranked in the top 15 graduate engineering schools in France and the top 500 universities worldwide.

The 2023-2027 strategy of Mines Saint-Etienne is in line with that of _Institut Mines Telecom_. It aims to:
- Support the ecological, digital and generational transitions and educate the people involved
- Support national and European sovereignty in microelectronics and digital technolog

To support this strategy, it is recruiting a PhD student.

**JOB DESCRIPTION**:
Advanced in vitro Ear-Nose-Throat (ENT) respiratory models: development of cellularized anatomical models for cell culture air-liquid exposure to enhance in vitro-in vivo correlation of intranasal drugs.

The position is based on the Saint-Étienne campus.

**Host laboratory**:
**Scientific context**:
In vitro respiratory 3D replicas serve as invaluable tools for investigating aerosol transport and deposition of intranasal drugs. By providing precise control over experimental conditions, these replicas enable detailed analysis of aerosol deposition patterns. However, limitations exist in terms of anatomical complexity and physiological relevance. Establishing a robust correlation between in vitro and in vivo (IVIVC) results is crucial for the development of novel inhaled drug delivery systems. The complexity of the respiratory tract, inter-individual variability, and challenges in measuring local aerosol deposition have hindered the establishment of such correlations. The project will identify and compare the key parameters that influence the deposition and absorption of drugs delivered into the nasal cavity by intranasal spray technologies. Through a multidisciplinary translational approach, this project aims to evaluate and compare the performance of a range of spray technologies in terms of (i) aerosol physical properties (droplet size, delivered dose and spray geometry), (ii) deposition zone in segmented nasal casts as a function of insertion angle and depth and drug formulation, (iii) in situ absorption of drugs on innovative cellularized nasal casts. Then, in vitro data will be used to build a predictive pharmacokinetic model, which will be further refined by integrating in vivo pharmacokinetic data from a clinical trial.

**Work plan**:
The project is divided into work packages (WP) requiring a wide range of complementary expertise in the field of aerosol metrology, industrial design, pharmacokinetics, in silico predictive model and nasal aerosol deposition.

**WP1 - Development of dismountable segmented nasal casts**: Nasal casts will be 3D-printed from CT scans of patients representing two population groups: infants and adults. The nasal impressions are segmented to cover all regions of drug deposition (nasal vestibule, nasal valve, turbinates (inferior, middle and superior) and posterior nasopharynx). The nasal casts will be dismountable to allow full access to the region and the future development of cellularized nasal casts.

**WP2 - Regional aerosol deposition in segmented nasal casts**:The intranasal regional deposition of the aerosol generated with selected nasal sprays will be assessed in segmented nasal casts (developed in WP1) using multiple markers (fluorimetric and drug dosage after washing of selected anatomical regions) according to different insertion angle and depth.

**WP3 - Development of cellularized nasal cast and In situ pharmacokinetics (PK) of intranasal drugs**:Segmented nasal casts are modified to incorporate docking areas determined from deposition data WP2 into the plug culture insert containing epithelial cells cultured at the air-liquid interface. Nasal sprays that have achieved optimal deposition in the selected anatomical regions according to the insertion parameters determined in WP2 are used to generate aerosols.

**WP4 - Building a predictive Physiologically Based PharmacoKinetic (PBPK) model**:A PBPK model will be built and parameterized to predict the systemic absorption of nasally administered drugs. The model is first parameterized with data available in the literature and then refined with empirical data generated from WP3.

**Objective and supervision**:
The objective of this doctoral thesis is to achieve the WP of the project. Bes