title: Totally S-protected hyaluronic acid: Evaluation of stability and mucoadhesive properties as liquid dosage form.
abstract: OBJECTIVE
  It is the aim of this study to synthesize hyaluronic acid (HA) derivatives bearing mucoadhesive properties and showing prolonged stability at pH 7.4 and under oxidative condition as liquid dosage form.
  
  
  METHODS
  HA was modified by thiolation with l-cysteine (HA-SH) and by conjugation with 2-mercaptonicotinic acid-l-cysteine ligand to obtain an S-protected derivative (HA-MNA). The polymers were characterized by determination of thiol group content and mercaptonicotinic acid content. Cytotoxicity, stability and mucoadhesive properties (rheological evaluation and tensile test) of the polymers were evaluated.
  
  
  RESULTS
  HA-SH and HA-MNA could be successfully synthesized with a degree of modification of 5% and 9% of the total moles of carboxylic acid groups, respectively. MTT assay revealed no toxicity for the polymers. HA-SH resulted to be unstable both at pH 7.4 and under oxidative conditions, whereas HA-MNA was stable under both conditions. Rheological assessment showed a 52-fold and a 3-fold increase in viscosity for HA-MNA incubated with mucus compared to unmodified HA and HA-SH, respectively. Tensile evaluation carried out with intestinal and conjunctival mucosa confirmed the higher mucoadhesive properties of HA-MNA compared to HA-SH.
  
  
  CONCLUSIONS
  According to the presented results, HA-MNA appears to be a potent excipient for the formulation of stable liquid dosage forms showing comparatively high mucodhesive properties.
authors: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors: Irene
authors: I
authors: Pereira de Sousa
authors: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors: Wongsakorn
authors: W
authors: Suchaoin
authors: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors: Ožbej
authors: O
authors: Zupančič
authors: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors: Christina
authors: C
authors: Leichner
authors: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: Andreas.Bernkop@uibk.ac.at.
authors: Andreas
authors: A
authors: Bernkop-Schnürch
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival; D006801:Humans; D006820:Hyaluronic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration
chemical_list: D006820:Hyaluronic Acid
keywords: Biological barrier; Liquid dosage form; Mucoadhesion; Preactivation; Thiolation