Synthesis and in vitro characterization of a preactivated thiomer via polymerization reaction.
The objective of this study was to synthesize 6-(2-acryloylamino-ethyldisulfanyl)-nicotinic acid (ACENA) for subsequent copolymerization with acrylic acid (AA) as a new method for synthesis of preactivated thiomers. Copolymerization reactions of ACENA and AA with different molar ratios were performed and the molecular weight (M(w)) values of the resulting copolymers were calculated and reported from 3046 to 3271 Da. The disulfide bond content values in the polymer chain were determined from 400 to 544 μmol disulfide bond per gram polymer. The transport enhancement ratio for 0.5% (m/v) solution of poly(acrylic acid) (PAA) was 1.1 using sodium fluorescein (Na-Flu) as model drug, in Ussing-type chambers, whereas it was over 1.9 for 0.5% (m/v) solution of ACENA and AA copolymers. Resazurin cell-viability test showed no significant toxicity for the polymers. Copolymerization of AA and disulfide-bond-containing monomers can open new horizons for the preparation of preactivated thiomers taking the better controllability and the huge variety of available monomers and combinations thereof into account.
Center for Chemistry and Biomedicine, Innsbruck, Austria.
Laleh
L
Solhi
Stefan A
SA
Schönbichler
Sarah
S
Dünnhaupt
Jan
J
Barthelmes
Heike
H
Friedl
Christian W
CW
Huck
Andreas
A
Bernkop-Schnürch
D000179:Acrylates / Q000737:chemistry / Q000494:pharmacology; D000180:Acrylic Resins / Q000138:chemical synthesis / Q000737:chemistry; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D019793:Fluorescein / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D008970:Molecular Weight; D009539:Nicotinic Acids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D058105:Polymerization; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
D000179:Acrylates; D000180:Acrylic Resins; D004220:Disulfides; D009539:Nicotinic Acids; D013438:Sulfhydryl Compounds; C006903:carbopol 940; C036658:acrylic acid; D019793:Fluorescein