Synthesis and In Vitro Characterization of a Preactivated Thiomer via Polymerization Reaction

• Published in: Biomacromolecules Vol. 13; no. 10; pp. 3054 - 3063
• Main Authors: Solhi, Laleh, Schönbichler, Stefan A, Dünnhaupt, Sarah, Barthelmes, Jan, Friedl, Heike, Huck, Christian W, Bernkop-Schnürch, Andreas
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 08-10-2012
• Subjects: Acrylates - chemistry; Acrylates - pharmacology; Acrylic Resins - chemical synthesis; Acrylic Resins - chemistry; Applied sciences; Biological and medical sciences; Caco-2 Cells; Cell Survival - drug effects; Disulfides - chemical synthesis; Disulfides - chemistry; Disulfides - pharmacology; Exact sciences and technology; Fluorescein - chemistry; General pharmacology; Humans; Medical sciences; Molecular Structure; Molecular Weight; Nicotinic Acids - chemical synthesis; Nicotinic Acids - chemistry; Nicotinic Acids - pharmacology; Organic polymers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; Polymerization; Polymers with particular properties; Preparation, kinetics, thermodynamics, mechanism and catalysts; Structure-Activity Relationship; Sulfhydryl Compounds - chemical synthesis; Sulfhydryl Compounds - chemistry; Sulfhydryl Compounds - pharmacology; Biological properties; Drug; Acrylic acid copolymer; Rat; Rodentia; Gut; Oral administration; Cytotoxicity; Acrylamide derivative copolymer; Bioavailability; Experimental study; Sulfur copolymer; In vitro; In vivo; Vertebrata; Organic disulfide; Mammalia; Animal; Preparation; Absorption enhancer; Acid copolymer; Radical copolymerization; Nicotinic acid derivatives
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm300788d

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.