Phospholipids as multifunctional material to treat fibrosis and inflammation

The treatment of fibrosis and inflammation is hindered by the complex nature of these conditions, making it challenging to develop targeted and effective interventions. To address this unmet clinical need, our research group tailored lipid-based drug delivery strategies for treating various fibrotic and inflammatory pathologies. 

We showed that bioactive polyenylphosphatidylcholines (PPCs) can revert activated, profibrogenic hepatic stellate cells (HSC) to a deactivated, quiescent-like status [1] and that the antifibrotic features of our PPC treatments can be transferred from the parent cells to resulting extracellular vesicles [2]. We also demonstrated that PPC-rich phosphatidylcholine can be combined with vitamin E and water to create a lipid mesophase-based ink suitable to produce 3D-printed tablets (printlets) [3]. These printlets remain intact in acidic conditions but disintegrate upon contact with intestinal fluids, enhancing the solubility of drugs without compromising the viability and permeability of intestinal epithelial cells. 

We revealed that the controlled aggregation of negatively charged liposomes enhances the lubrication properties of the resulting liposomal depots. These findings pave the way for a novel local treatment of osteoarthritis, a debilitating chronic joint disease characterized by degradation of articular cartilage, synovial fibrosis, and low-grade inflammation [4]. 

Lastly, to treat peritoneal pathologies locally, we loaded liposomes with a tyrosine kinase inhibitor and incorporated the vesicles in 3D-printed μbeads [5]. This multicomposite system, designed for intraperitoneal administration, could reduce the clearance of drugs administered in the peritoneal cavity to treat post-surgical adhesions, peritoneal carcinomatosis, or peritoneal fibrosis.

References:

[1] Skorup et al. Int. J. Pharm. 2023, 646:123473.

[2] Zivko et al. Eur. J. Pharm. Biopharm. 2023, 182:32-40.

[3] Carone et al. Adv. Mater. Technol. 2024, 2301930.

[4] G. Bordon et al. J. Colloid Interface Sci. 2023, 650:1659-1670.

[5] Eugster et al. Drug Deliv. Transl. Res. 2024, 14:1567-1581.