Project: Pre-clinical development of an acylceramide nanostructured delivery system to rescue the skin barrier in patients with ichthyosis

Acronym	LIPARCI (Reference Number: EURONANOMED2021-095)
Duration	01/01/2022 - 31/12/2024
Project Topic	Inherited ichthyoses are rare genetic diseases (prevalence 13.3 per million people in Europe) that occur at birth. They cause abnormal thickening of the skin, dryness, scaling, redness, itching and painful skin fissures involving life-long disfigurement and social ostracism. All forms of ichthyosis lead to a defective epidermal barrier and more than half of patients shows Autosomal Recessive Congenital Ichthyosis (ARCI) in which the metabolism of ?-O-acylceramides is impaired. This lipid species and, more precisely, linoleic acid (LA) esterified to ?-hydroxyacyl sphingosine (CerEOS), are essential for building a healthy stratum corneum (SC), the outermost epidermal layer responsible for the skin barrier. Current treatments of the ichthyoses are mainly symptomatic, untargeted, often minimally effective and with significant side effects. Thus, replacement of the missing ceramides is a promising therapeutic approach. The peculiar structure of the CerEOS quintessentially containing esterified LA seems fundamental for proper skin repair. However, the low solubility and extreme lipophilicity of CerEOS are challenging for its chemical synthesis and delivery to deeper SC to reach full effect. Moreover, the nanoscale organization of the SC makes difficult the entry of substances. This justifies an approach based on nanotechnology that allows the delivery of the mentioned lipids in the place where they have their biological function. The aim of LIPARCI is to develop an innovative lipid substitution system based on synthetic LA-esterified CerEOS and LA-esterified ?-hydroxy fatty acids included in nanostructured lipid systems that will be validated for rescuing the epidermal barrier using pre-clinical in vitro and animal models of ichthyosis. LIPARCI should thus allow the future development of highly efficient pathogenesis-based therapy of ichthyoses exhibiting impaired CerEOS metabolism as a primary defect.
Website	visit project website
Network	EuroNanoMed III
Call	Joint Transnational Call (2021)

Project partner

Number	Name	Role	Country
1	INSERM UMR1291 - CNRS UMR5051 - Université Toulouse III	Coordinator	France
2	Institute of Advanced Chemistry of Catalonia-Spanish National Research Council	Partner	Spain
3	Hospital Infantil Niño Jesús	Partner	Spain
4	Charles University, Faculty of Pharmacy in Hradec Kralove	Partner	Czech Republic
5	Bezmialem Vakif University	Partner	Türkiye