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 fromFlavobacterium 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 throughin vitrostudies 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. [ABSTRACT FROM AUTHOR]
Norsa, Lorenzo, Tomba, Carolina, Agostoni, Carlo, Branchi, Federica, Bardella, Maria Teresa, Roncoroni, Leda, Conte, Dario, and Elli, Luca
Subjects
CELIAC disease treatment, GLUTEN-free diet, CELIAC disease in children, QUALITY of life, GASTROENTEROLOGY
Abstract
Objectives: Celiac disease (CD) is treated by life-long gluten-free diet (GFD). Novel therapies are under development. Willingness of CD children's parents to alternative therapies and GFD impact were evaluated. Methods: Parents of celiac children on GFD were investigated on need and preference for novel CD therapies, children's enrolment in trials, compliance to and personal judgment on GFD, health status (HS) and quality of life (QoL). Results: About 59.5% surveyed parents expressed the need for alternative therapies with a preference for vaccine-based strategy (39.9%). About 37.7% would accept enrollment in an ad hoc trial, 20.3% would agree to endoscopy during the trial. GFD compliance was 97.4% and well accepted by 93.8%. HS and QoL significantly improved during GFD ( p < 0.001). Conclusions: The introduction of novel therapies for CD is desirable for over half of parents, with preference for vaccines. Parents frown upon enrolment in new clinical trials and the subsequent need for additional endoscopy. [ABSTRACT FROM AUTHOR]