title: Combination of SEDDS and Preactivated Thiomer Technology: Incorporation of a Preactivated Thiolated Amphiphilic Polymer into Self-Emulsifying Delivery Systems.
abstract: The aim of the study was to create novel mucoadhesive drug delivery systems by incorporating amphiphilic hydrophobically modified, thiolated and preactivated polymers (preactivated thiomers) into self-emulsifying drug delivery systems (SEDDS).
  
  
  
  L-Cysteine methyl ester was covalently attached to the polymeric backbone of Pemulen TR-2 and preactivated using 2-mercaptonicotinic acid (2-MNA). These thiomers were incorporated in a concentration of 0.3% (w/v) into SEDDS. The size distribution and the zeta potential of the emulsions were evaluated by dynamic light scattering. Mucoadhesive properties of thiomers-SEDDS spiked with FDA (fluorescein diacetate) were examined utilizing rheological measurement, permeation studies and in vitro residence time study on porcine mucosa. Cell viability tests were additionally performed.
  
  
  
  734 ± 58 μmol L-Cysteine methyl ester and 562 ± 71 μmol 2-MNA could be attached per gram polymer of Pemulen TR-2. Emulsions exhibited a droplet size range between 180 and 270 nm. Blank SEDDS possessed a zeta potential value between -5.7 and -8.6 mV, whereas thiomers-SEDDS between -14.6 and -17.2 mV. Viscous modulus of thiomer and preactivated thiomer containing SEDDS-mucus mixture was 8-fold and 11-fold increased in comparison to reference. The amount of FDA permeated the mucus layer was 2-fold lower in case of thiomers-SEDDS compared to blank SEDDS. A prolonged residence time was observed for thiomers-SEDDS over 45 min. During cell viability studies no severe toxic effects were detected.
  
  
  
  The novel developed SEDDS with incorporated thiomers might be a promising tool for mucoadhesive oral drug delivery.
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH,, Innsbruck, Austria.
authors.forename: Gergely
authors.initials: G
authors.lastname: Hetényi
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH,, Innsbruck, Austria.
authors.forename: Janine
authors.initials: J
authors.lastname: Griesser
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH,, Innsbruck, Austria.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Nardin
authors.affiliation: Thiomatrix Forschungs-und Beratungs GmbH,, Innsbruck, Austria. andreas.bernkop@uibk.ac.at.|Department of Pharmaceutical Technology, Center for Chemistry and Biomedicine, Institute of Pharmacy, Leopold-Franzens-University, Innrain 80/82, 6020, Innsbruck, Austria. andreas.bernkop@uibk.ac.at.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002448:Cell Adhesion; D002470:Cell Survival; D003545:Cysteine / Q000031:analogs & derivatives / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007413:Intestinal Mucosa / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D009539:Nicotinic Acids / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability; D011108:Polymers / Q000737:chemistry*; D012212:Rheology; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013499:Surface Properties; D013552:Swine
chemical_list: D004655:Emulsions; D009539:Nicotinic Acids; D011108:Polymers; D013438:Sulfhydryl Compounds; C083470:2-mercaptonicotinic acid; D003545:Cysteine; C017507:mecysteine
keywords: mucoadhesive SEDDS; mucoadhesive drug delivery; nanocarrier; preactivated thiomer; self-emulsifying drug delivery systems