ASSESSING SUBCUTANEOUS INJECTION SITE REACTIONS

by leveraging immunocompetent human skin & artificial intelligence

A study using the HypoSkin® model

IDENTIFYING COMPOUNDS THAT TRIGGER INJECTION SITE REACTIONS

The Research in this study was carried out by Genoskin’s Emeline Pagès, Emilie Braun, Eric Merle (CBIO), Pascal Descargues (CEO), Nicolas Gaudenzio (CSO) and presented in a scientific poster at the Controlled Release Society‘s 2021 Virtual Annual Meeting that took place from July 25 to 29, 2021.

Upon subcutaneous injection of therapeutic formulations, a fast and local inflammatory reaction typically characterized by erythema, swelling and pain can develop at the injection site and is commonly named “injection site reaction” (i.e. ISR). The identification of safer next-generation drug candidates that do not trigger an ISR represents a major challenge in the field. Here we use stabilized immunocompetent healthy-looking human skin explants from multiple donors of different age and sex to assess the extent to which therapeutic molecules are susceptible to trigger mast cell-dependent and mast cell-independent ISR-like inflammatory responses at the site of injection.

Combining Immunocompetent Human Skin & Artificial Intelligence

FOCUS ON MAST CELL DEGRANULATION

To conduct this study, the Genoskin team used HypoSkin® models and injected them with 3 different substances for study and control purposes. The models were then processed to analyse mast cell degranulation and placed under a fluorescent microscope. Subsequently, they were submitted to Genoskin’s algorithms to enable the automated detection of mast cell granules distribution and unbiased in situ analysis of the samples.

Mast cell granules in injected Hyposkin models

AVIDIN-BASED STAINING OF IN SITU MAST CELLS UPON SUBCUTANEOUS INJECTION. HypoSkin® models were injected subcutaneously with 100 µL of water control (A) or 0.5 mg/mL of compound 48/80 (c48/80) (B) or 0.5 mg/mL (clinical concentration injected subcutaneously in patients) of Drug 1 (C). 5 µm tissue sections were then stained with 10 µg/mL of Sulforhodamine 101-labelled avidin (Avidin; red).

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