Formulation of extracellular vesicles by spray-drying for the treatment of inflammatory lung di[...]

Université Paris-Saclay; Paris; Sur place; EUR 40 000 - 60 000; Plein temps

Résumé du poste

A prestigious university in Paris is offering an internship focusing on the formulation of extracellular vesicles into dry powder for inhalation. The candidate will gain experience in spray-drying techniques and EV characterization while contributing to innovative research in respiratory disease therapies. Candidates should have an academic background in relevant fields and a strong motivation for hands-on experimentation.

Qualifications

• Candidates must have an academic background related to the project.
• A strong motivation for experimentation and teamwork is essential.

Responsabilités

• Spray-dry EVs into solid microparticles for lung delivery.
• Characterize EVs before and after spray-drying.
• Evaluate EV immunosuppressive properties.

Connaissances

Academic training in pharmacy, biotechnologies, biomedical engineering, physical chemistry

High motivation for multidisciplinary research

Strong appetite for experimentation

Team spirit

Formation

Relevant academic training

Description du poste

Description

Host laboratory

Institut Galien Paris-Saclay, Université Paris Saclay

Henri Moissan building

17 avenue des Sciences

Orsay

Supervisors: Marine Le Goas / Co-supervision by Nicolas Tsapis

Internship period: 1st semester

The candidate must already be in France.

Project description

Context of the project

Respiratory diseases are a major public health issue, ranking as the third leading cause of death worldwide. Specifically, the prevalence of inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, and fibrosis has increased over the past few decades. Inhaled corticosteroids are currently used to alleviate symptoms and slow disease progression. However, these drugs may cause side effects and lead to resistance. This situation underscores the need to develop new anti-inflammatory treatments as alternatives to corticosteroids. Extracellular vesicles (EVs) are a promising avenue, especially those produced by mesenchymal stem cells (MSCs), which have already shown anti-inflammatory properties in the lungs. Their delivery to the lungs remains challenging, as their small size (diameter around 50- nm) prevents them from effectively reaching the bronchi and alveoli.

Objectives

This project aims to formulate EVs into a dry powder suitable for lung delivery by inhalation. Our strategy is to apply spray-drying to EV suspensions to obtain micron-sized particles, as already proposed for nanoparticles.

The objectives of the internship are the following:

• Spray-drying of EVs into solid microparticles optimized for lung delivery (size between 1 and 5 µm)
• Characterization of EVs before and after spray-drying to ensure preservation of their biophysical properties
• In vitro evaluation of EV immunosuppressive properties before and after spray-drying

Scientific program

The intern will learn and apply the following methodologies to answer the 3 objectives.

1. Spray-drying of EVs into solid microparticles optimized for lung delivery

Model EVs extracted from bovine milk will be mainly used. They will be spray-dried under various conditions, varying the composition (excipients and excipient / EV ratio) and process parameters (drying temperature). The size of the resulting powders will be characterized by laser granulometry, and their morphology by scanning electron microscopy (SEM). Their aerosolization will be assessed by a Next Generation Impactor (NGI) as detailed in the European Pharmacopeia.

2. Characterization of EVs before and after spray-drying to ensure preservation of their biophysical properties

EV concentration and size will be measured by nanoparticle tracking analysis (NTA). Their zeta potential will be determined by electrophoretic mobility, and their morphology will be observed by transmission electron microscopy (TEM). Various biochemical assays will be used to evaluate the total quantity of proteins and nucleic acids. The presence of EV-specific markers may also be investigated using Western Blot assays. Long-term stability under various storage conditions will also be studied.

3. In vitro evaluation of EV immunosuppressive properties before and after spray-drying

In this part, MSC-derived EVs will be used. The spray-drying parameters may need to be tuned for this new type of EVs. In vitro tests will be performed with a model of inflammation obtained by exposure of macrophages to lipopolysaccharides. The anti-inflammatory properties of plain and spray-dried EVs will be compared by studying macrophage polarization in this model.

References

1. Monsel A, Zhu Y, Gudapati V, et al. Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases.

2. Khalaj K, Figueira RL, Antounians L, et al. Systematic review of extracellular vesicle-based treatments for lung injury : are EVs a potential therapy for COVID-19? J Extracell Vesicles ; 9 : .

3. Tsapis N, Bennett D, Jackson B, et al. Trojan particles : Large porous carriers of nanoparticles for drug delivery. Proc Natl Acad Sci ; 99 : –.

4. Gómez-Gaete C, Fattal E, Silva L, et al. Dexamethasone acetate encapsulation into Trojan particles. J Controlled Release ; : 41–49.

5. Bohr A, Tsapis N, Foged C, et al. Treatment of acute lung inflammation by pulmonary delivery of anti-TNF-α siRNA with PAMAM dendrimers in a murine model. Eur J Pharm Biopharm ; : –.

Profile

• Academic training in one of the following fields: pharmacy, biotechnologies, biomedical engineering, physical chemistry
• High motivation to carry out a multidisciplinary research project at the interface of pharmaceutical formulation, physical chemistry, and biology
• Strong appetite for experimentation
• Team spirit

Starting date

• 02-01