title: A methacrylic hyaluronic acid derivative for potential application in oral treatment of celiac disease.
abstract: 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.
authors.affiliation: a Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche , Università degli Studi di Palermo , Palermo , Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Pitarresi
authors.affiliation: b Institute of Biophysics at Palermo , Italian National Research Council , Palermo , Italy.
authors.forename: Fabio Salvatore
authors.initials: FS
authors.lastname: Palumbo
authors.affiliation: b Institute of Biophysics at Palermo , Italian National Research Council , Palermo , Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Triolo
authors.affiliation: b Institute of Biophysics at Palermo , Italian National Research Council , Palermo , Italy.
authors.forename: Calogero
authors.initials: C
authors.lastname: Fiorica
authors.affiliation: a Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche , Università degli Studi di Palermo , Palermo , Italy.|b Institute of Biophysics at Palermo , Italian National Research Council , Palermo , Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Giammona
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002446:Celiac Disease / Q000188:drug therapy* / Q000473:pathology; D005029:Ethylenediamines / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000494:pharmacology*; D020100:Hydrogels / Q000737:chemistry*; D008689:Methacrylates / Q000008:administration & dosage* / Q000494:pharmacology*; D051379:Mice; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000737:chemistry*
chemical_list: D005029:Ethylenediamines; D020100:Hydrogels; D008689:Methacrylates; C008384:methacrylic acid; C031234:ethylenediamine; D006820:Hyaluronic Acid; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases
keywords: Hyaluronic acid; UV irradiation; celiac disease; oral enzyme release; prolyl endopeptidase