Characterization of aerosol released from abrasion of 2D material reinforced composites and in vitro safety assessment of abraded particles on human lung and gastrointestinal cell cultures

External project at EMPA, St. Gallen, Switzerland in cooperation with Prof. Dr. Scott McNeil and Prof. Dr. Jörg Huwyler

Further information and project description

Lysosomal storage diseases are pathologies caused by mutations in lysosomal hydrolases. They are serious metabolic disorders, that can lead to major physical or cognitive impairments. Replacement of endogenous dysfunctional enzymes with recombinant versions through blood infusions is the current standard of care. However, immune reactions result in neutralization of these therapeutic enzymes and severely decrease the efficacy of treatment.
Incorporating pharmaceuticals into‘nanoformulations’has been shown to decrease these adverse immune reactions.  The Nanopharmaceutical and Regulatory Sciences Group is encapsulating lysosomal hydrolases into nanoformulations, with the goal of improving the enzymes’ biocompatibility and overall PK/PD profile.In this important and contributing project,the student will produce and characterize these enzyme-containing nanoformulations. They will evaluate the formulations for immunocompatibility, using biomarkers ofimmunogenicity. The student will also become proficient with the various methods and instruments used to evaluate nanoformulations, such as DLS, ELISA, and flow cytometry. Results obtained in this project are intended to help optimize these novel formulations, and to overcome the adverse immune response. 

The Nanopharmaceutical and Regulatory Sciences Group has openings for two students, to produce and characterize nanoformulations. The formulations will encapsulate recombinant enzymes, for the treatment of lysosomal storage disorders, such as Pompe Disease, Sanfilippo syndrome, and Tay-Sachs. For these diseases, the parenteral administration of recombinant enzymesis the current standard of care. This treatment is not without limitations, however, as the ‘naked’ enzymes quickly develop anti-drug antibodies (ADA), which severely impact the enzymes’ bioavailability and biodistribution.
The goal of this project is to incorporate the enyzmes into‘nanoformulations’, to decrease these adverse events.In this important project,the student will synthesize and rigorously characterize enzyme-containing nanoformulations. The formulations will be optimized for their biocompatibility, PK/PD profile, and their ability to target the affected cells. The student will become proficient with the various methods and instruments used to characterize nanoformulations, such as DLS, U/HPLC-ELSD, and fluorescence microscopy. Results obtained in this project will contribute to the development of novel therapies for these devastating diseases.