title: Novel pectin-4-aminothiophenole conjugate microparticles for colon-specific drug delivery.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 52, Josef-Möller-Haus, 6020 Innsbruck, Austria.
authors.forename: Glen
authors.initials: G
authors.lastname: Perera
authors.forename: Jan
authors.initials: J
authors.lastname: Barthelmes
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D003106:Colon / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008795:Metronidazole / Q000008:administration & dosage* / Q000494:pharmacology; D010316:Particle Size; D010368:Pectins / Q000138:chemical synthesis / Q000737:chemistry*; D013438:Sulfhydryl Compounds
chemical_list: D000814:Aniline Compounds; D000890:Anti-Infective Agents; D013438:Sulfhydryl Compounds; D008795:Metronidazole; D010368:Pectins; C064316:4-aminothiophenol