pectins and 4-aminothiophenol

The aim of this study was to modify pectin by covalent attachment of the water-insoluble ligand 4-aminothiophenol to its polymeric backbone. 4-Aminothiophenol is a ligand which is highly prone to oxidation. Therefore, this ligand allows oxidative cross-linking of pectin under mild oxidative conditions. Additionally, hydrophobization of pectin can be achieved by the mentioned modification which offers certain advantages over highly hydrophilic native pectins. 4-Aminothiophenol was covalently attached to pectin via amide bond formation between carboxylic moieties of pectin and the amino-group of 4-aminothiophenol. Two different pectin-4-aminothiophenol conjugates were synthesized and investigated regarding the amount of coupled ligand, rheological behavior under oxidative conditions, swelling behavior, and cytotoxic effects. Within this study, 557.3 +/- 49.0 and 158.8 +/- 23.1 micromol 4-aminothiophenol have been coupled per gram pectin. Within both conjugates, around 75% of the bound ligand appeared in its reduced form. Within rheological studies, a 500-fold increase in viscosity was achieved by addition of hydrogen peroxide as an oxidizing agent. Investigations on the swelling behavior revealed that this hydrophobic modification of pectin results in decelerated water uptake on the one hand and improved cohesive properties after oxidation of thiol groups to disulfide bonds on the other hand. Thereby, the maximum amount of water which can be uptaken by pectin matrices could be increased. According to these results, Pec-ATP conjugates could be valuable tools for several pharmaceutical applications due to the established method of gelation and the altered swelling and disintegration behavior.

Topics: Aniline Compounds; Hydrophobic and Hydrophilic Interactions; Oxidation-Reduction; Pectins; Polymers; Rheology; Sulfhydryl Compounds; Viscosity; Water

Within this study metronidazole-containing microparticles based on a pectin-4-aminothiophenol (Pec-ATP) conjugate were developed and investigated regarding their potential for colon-specific drug delivery. Microparticles were produced by spray-drying and subsequent processing. Posteriorly, they were investigated regarding their disintegration behavior, particle size, drug load, release behavior and impact on viability of Caco-2 cells. Microparticles with a mean diameter of 5.16+/-2.41 microm and a drug load of 1.15+/-0.03% metronidazole were prepared. Disintegration studies revealed that the stability of Pec-ATP microparticles was significantly improved compared to control microparticles based on unmodified pectin. In vitro release studies without potential colonic release-inducers revealed that 34.4-fold more metronidazole is retarded in Pec-ATP microparticles within 6h compared to control particles. It could be demonstrated that the retarded amount of metronidazole can be released rapidly under the influence of pectinolytic enzymes or a reducing agent, simulating the colonic environment. Cell viability studies did not reveal a significant difference between native and modified pectin, neither as a solution nor as microparticle suspension. From the improved stability, the described release features and the low toxicity of the investigated microparticles can be concluded that these particles are a promising carrier for colon-specific drug delivery.

Topics: Aniline Compounds; Anti-Infective Agents; Caco-2 Cells; Cell Survival; Colon; Drug Delivery Systems; Humans; Metronidazole; Particle Size; Pectins; Sulfhydryl Compounds