title: Pectin-cysteine conjugate: synthesis and in-vitro evaluation of its potential for drug delivery.
abstract: This study was aimed at improving certain properties of pectin by introduction of thiol moieties on the polymer. Thiolated pectin was synthesized by covalent attachment of cysteine. Pectin-cysteine conjugate was evaluated for its ability to be degraded by pectinolytic enzyme. The toxicity profile of the thiolated polymer in Caco-2-cells, its permeation enhancing effect and its mucoadhesive and swelling properties were studied. Moreover insulin-loaded hydrogel beads of the new polymer were examined for their stability in simulated gastrointestinal conditions and their drug release profile. The new polymer displayed 892.27 +/- 68.68 micromol thiol groups immobilized per g polymer, and proved to have retained its biodegradability, upon addition of Pectinex Ultra SPL in-vitro, determined by viscosity measurements and titration method. Pectin-cysteine showed no severe toxicity in Caco-2 cells, as tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Moreover, the synthesized polymer exhibited a relative permeation enhancement ratio of 1.61 for sodium fluorescein, compared to unmodified pectin. Pectin-cysteine conjugate exhibited approximately 5-fold increased in in-vitro adhesion duration and significantly improved cohesive properties. Zinc pectin-cysteine beads showed improved stability in simulated gastrointestinal media; however, insulin release from these beads followed the same profile as unmodified zinc pectinate beads. Due to favourable safety and biodegradability profile, and improved cohesive and permeation-enhancing properties, pectin-cysteine might be a promising excipient in various transmucosal drug delivery systems.
authors.affiliation: Department of Pharmaceutics, Tehran University of Medical Sciences, Tehran 14174, Iran.
authors.forename: Sayeh
authors.initials: S
authors.lastname: Majzoob
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.forename: Farid
authors.initials: F
authors.lastname: Dorkoosh
authors.forename: Krum
authors.initials: K
authors.lastname: Kafedjiiski
authors.forename: Brigitta
authors.initials: B
authors.lastname: Loretz
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D018938:Caco-2 Cells; D002234:Carbodiimides / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D003545:Cysteine / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D019793:Fluorescein / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D015394:Molecular Structure; D010368:Pectins / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D011096:Polygalacturonase / Q000378:metabolism; D015203:Reproducibility of Results; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D014783:Viscosity
chemical_list: D002234:Carbodiimides; D004364:Pharmaceutical Preparations; D013438:Sulfhydryl Compounds; C074139:1-ethyl-3-(3-dimethylaminoethyl)carbodiimide; D010368:Pectins; D011096:Polygalacturonase; D003545:Cysteine; D019793:Fluorescein