Pectin-cysteine conjugate: synthesis and in-vitro evaluation of its potential for drug delivery.
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.
Majzoob
Sayeh
S
Department of Pharmaceutics, Tehran University of Medical Sciences, Tehran 14174, Iran.
Atyabi
Fatemeh
F
Dorkoosh
Farid
F
Kafedjiiski
Krum
K
Loretz
Brigitta
B
Bernkop-Schnürch
Andreas
A
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
D002234:Carbodiimides; D004364:Pharmaceutical Preparations; D013438:Sulfhydryl Compounds; C074139:1-ethyl-3-(3-dimethylaminoethyl)carbodiimide; D010368:Pectins; D011096:Polygalacturonase; D003545:Cysteine; D019793:Fluorescein