title: Self-emulsifying drug delivery systems (SEDDS): Proof-of-concept how to make them mucoadhesive.
abstract: OBJECTIVE
  The objective of this study was to provide a proof-of-concept that self-emulsifying drug delivery systems can be made mucoadhesive by the incorporation of hydrophobic mucoadhesive polymers.
  
  
  METHODS
  In order to obtain such a hydrophobic mucoadhesive polymer, Eudragit® S100 was thiolated by covalent attachment of cysteamine. After determination of the thiol group content, in vitro mucoadhesion studies (rotating cylinder and rheological measurements) were performed. Then, synthesized conjugate was incorporated into self-emulsifying drug delivery systems (SEDDS) and their toxic potential as well as that of unmodified and thiolated Eudragit® S100 was examined on Caco-2 cell line. Lastly, the mucoadhesiveness of developed SEDDS on porcine intestinal mucosa was determined.
  
  
  RESULTS
  Generated thiolated Eudragit® S100 displaying 235±14μmol of free thiol groups and 878±101μmol of disulfide bonds per gram polymer showed a great improvement in both: dynamic viscosity with mucus and adhesion time on mucosal tissue compared to the unmodified polymer. Resazurin assay revealed that unmodified and thiolated polymers and also SEDDS dispersions were non-toxic over Caco-2 cells. Furthermore, the incorporation of 1.5% (w/w) of such thiomer into SEDDS led to remarkably improved mucoadhesiveness. Blank SEDDS were completely removed from the mucosa within 15min, whereas >60% of SEDDS containing thiolated Eudragit® S100 were still attached to it.
  
  
  CONCLUSIONS
  These results provide evidence that SEDDS can be made mucoadhesive by the incorporation of hydrophobic mucoadhesive polymers.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Chemistry and Biomedicine, Leopold - Franzens University Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Gintare
authors.initials: G
authors.lastname: Leonaviciute
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Chemistry and Biomedicine, Leopold - Franzens University Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Nada Trivic
authors.initials: NT
authors.lastname: Adamovic
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Chemistry and Biomedicine, Leopold - Franzens University Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Hung Thanh
authors.initials: HT
authors.lastname: Lam
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Chemistry and Biomedicine, Leopold - Franzens University Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Rohrer
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Chemistry and Biomedicine, Leopold - Franzens University Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Partenhauser
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Center for Chemistry and Biomedicine, Leopold - Franzens University Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000180:Acrylic Resins; D000818:Animals; D018938:Caco-2 Cells; D016503:Drug Delivery Systems; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D013552:Swine; D014014:Tissue Adhesives
chemical_list: D000180:Acrylic Resins; D014014:Tissue Adhesives; C050528:Eudragit RS
keywords: Cysteamine; Eudragit® S100; Mucoadhesion; Self-emulsifying system; Thiol group