A methacrylic hyaluronic acid derivative for potential application in oral treatment of celiac disease
- Autori: Pitarresi, G.; Palumbo, F.; Triolo, D.; Fiorica, C.; Giammona, G.
- Anno di pubblicazione: 2017
- Tipologia: Articolo in rivista (Articolo in rivista)
- Parole Chiave: celiac disease; Hyaluronic acid; oral enzyme release; prolyl endopeptidase; UV irradiation; Administration, Oral; Animals; Celiac Disease; Ethylenediamines; Humans; Hyaluronic Acid; Hydrogels; Methacrylates; Mice; Serine Endopeptidases; Pharmacology; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry
Objective: Aim of this work was the synthesis of a methacrylic hyaluronic acid (HA) derivative and the production, via photocrosslinking, of related hydrogels loaded with an endopeptidase intended for a potential oral treatment of celiac disease. Methods: The methacrylic derivative of HA was prepared through a one-pot procedure involving the reaction with ethylenediamine (EDA) and methacrylic anhydride (MA). The obtained derivative, named HA-EDA-MA, was used to prepare photocrosslinked hydrogels loaded with a prolyl endopeptidase derived from Flavobacterium meningosepticum (PEP FM) able to detoxify gliadin. Obtained hydrogels were recovered as gels or freeze-dried powders. Results: Hydrogels obtained as freeze-dried powders, are able to protect loaded enzyme from degradation due to freeze-drying process and from alteration during storage, overall in the presence of a cryoprotectant. All photocrosslinked HA-EDA-MA hydrogels (gels and powders) release PEP FM in simulated intestinal fluid in sustained manner and in active form. HA-EDA-MA hydrogels are nontoxic as demonstrated through in vitro studies on BALB 3T3 cells. Conclusions: Prepared hydrogels show a potential application for oral treatment of celiac disease thanks to the possibility to release enzymes able to detoxify the gliadin peptide that induces the immunogenic response.