Formulation of extracellular vesicles by spray-drying for the treatment of inflammatory lung diseases by inhalation

The Institut Galien Paris-Saclay (UMR CNRS 8612), founded in 1986, develops micro and nanotechnologies applied to medicine and diagnostics in the health field. The unique characteristic of the unit is to bring together academics from different disciplines (chemistry, physical chemistry, galenics, analytical chemistry, and biology). Our research themes are organized according to four major challenges:

1- Tame physiological barriers

2- Design intelligent, programmable, activable and biocompatible materials

3- Develop predictive models for the formation of new objects and their transport across biological barriers (tissue, cellular and subcellular)

4- Combine chemistry, physical chemistry and formulation for diagnostics and imaging purposes.

To address these challenges, the Institut Galien Paris-Saclay possesses a wide range of state-of-the-art research equipment gathered into several platforms driven by highly qualified scientific officers and technicians (chromatographic analysis, cell culture, manipulation of radio elements, instrumentation workshop, molecular interactions, rheology). The Institut Galien Paris-Saclay attracts every year a large number of doctoral students and post-doctoral researchers from around the world. We accommodates 3 members of the Institut Universitaire de France, 1 academic with an ERC grant, 5 members of the Academy of Pharmacy and 1 member of the Academy of Sciences. The current five-year period will see our move to the Saclay plateau, which will encourage new collaborations that we hope will be fruitful.

Host laboratory
Institut Galien Paris-Saclay, Université Paris Saclay
Henri Moissan building
17 avenue des Sciences
91190 Orsay

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

Internship period: 1^st semester 2026

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 in 2019. 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.^1,2 Their delivery to the lungs remains challenging, as their small size (diameter around 50-150 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.^3,4

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.

- 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.

- 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.

- 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.⁵ 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. Expert Opin Biol Ther 2016; 16: 859–871.

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 2020; 9: 1795365.

3.     Tsapis N, Bennett D, Jackson B, et al. Trojan particles: Large porous carriers of nanoparticles for drug delivery. Proc Natl Acad Sci 2002; 99: 12001–12005.

4.     Gómez-Gaete C, Fattal E, Silva L, et al. Dexamethasone acetate encapsulation into Trojan particles. J Controlled Release 2008; 128: 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 2020; 156: 114–120.

• 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