title: Can thiolation render a low molecular weight polymer of just 20-kDa mucoadhesive?
abstract: The objective was to investigate whether even low-molecular weight polymers (LMWPs) can be rendered mucoadhesive due to thiolation. Interceded by the double catalytic system carbodiimide/N-hydroxysuccinimide, cysteamine was covalently attached to a copolymer, poly(4-styrenesulfonic acid-co-maleic acid) (PSSA-MA) exhibiting a molecular weight of just 20 kDa. Depending on the amount of added N-hydroxysuccinimide and cysteamine, the resulting PSSA-MA-cysteamine (PC) conjugates exhibited increasing degree of thiolation, highest being "PC 2300" exhibiting 2300.16 ± 149.86 μmol thiol groups per gram of polymer (mean ± SD; n = 3). This newly developed thiolated polymer was evaluated regarding mucoadhesive, rheological and drug release properties as well from the toxicological point of view. Swelling behavior in 100 mM phosphate buffer pH 6.8 was improved up to 180-fold. Furthermore, due to thiolation, the mucoadhesive properties of the polymer were 240-fold improved. Rheological measurements of polymer/mucus mixtures confirmed results obtained by mucoadhesion studies. In comparison to unmodified polymer, PC 2300 showed 2.3-, 2.3- and 2.4-fold increase in dynamic viscosity, elastic modulus and viscous modulus, respectively. Sustained release of the model drug codeine HCl out of the thiomer was provided for 2.5 h (p < 0.05), whereas the drug was immediately released from the unmodified polymer. Moreover, the thiomer was found non-toxic over Caco-2 cells for a period of 6- and 24-h exposure. Findings of the present study provide evidence that due to thiolation LMWPs can be rendered highly mucoadhesive as well as cohesive and that a controlled drug release out of such polymers can be provided.
authors.affiliation: a Department of Pharmaceutical Technology , Institute of Pharmacy, University of Innsbruck , Innsbruck , Austria .
authors.forename: Arshad
authors.initials: A
authors.lastname: Mahmood
authors.affiliation: a Department of Pharmaceutical Technology , Institute of Pharmacy, University of Innsbruck , Innsbruck , Austria .
authors.forename: Sonja
authors.initials: S
authors.lastname: Bonengel
authors.affiliation: a Department of Pharmaceutical Technology , Institute of Pharmacy, University of Innsbruck , Innsbruck , Austria .
authors.forename: Flavia
authors.initials: F
authors.lastname: Laffleur
authors.affiliation: a Department of Pharmaceutical Technology , Institute of Pharmacy, University of Innsbruck , Innsbruck , Austria .
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ijaz
authors.affiliation: a Department of Pharmaceutical Technology , Institute of Pharmacy, University of Innsbruck , Innsbruck , Austria .
authors.forename: Muneeb Ahmad
authors.initials: MA
authors.lastname: Idrees
authors.affiliation: b Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck , Innsbruck , Austria , and.
authors.forename: Shah
authors.initials: S
authors.lastname: Hussain
authors.affiliation: b Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck , Innsbruck , Austria , and.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Huck
authors.affiliation: c Department of Pharmaceutical Chemistry , Institute of Pharmacy, University of Innsbruck , Innsbruck , Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Matuszczak
authors.affiliation: a Department of Pharmaceutical Technology , Institute of Pharmacy, University of Innsbruck , Innsbruck , Austria .
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000269:Adhesives / Q000737:chemistry*; D000818:Animals; D018938:Caco-2 Cells; D002234:Carbodiimides / Q000737:chemistry; D045744:Cell Line, Tumor; D003543:Cysteamine / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008298:Maleates / Q000737:chemistry; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry; D012212:Rheology; D013388:Succinimides / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013552:Swine; D014783:Viscosity
chemical_list: D000269:Adhesives; D002234:Carbodiimides; D008298:Maleates; D011108:Polymers; D011137:Polystyrenes; D013388:Succinimides; D013438:Sulfhydryl Compounds; C518261:poly(4-styrenesulfonic acid-co-maleic acid); D003543:Cysteamine; C001426:N-hydroxysuccinimide
keywords: Controlled release; mucoadhesion; poly(4-styrenesulfonic acid-co-maleic acid)–cysteamine conjugate; rheology; thiomers