Pectin-cysteine conjugate: synthesis and in-vitro evaluation of its potential for drug delivery

J Pharm Pharmacol. 2006 Dec;58(12):1601-10. doi: 10.1211/jpp.58.12.0006.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Carbodiimides / chemistry
  • Cell Survival / drug effects
  • Cysteine / chemistry*
  • Cysteine / metabolism
  • Drug Delivery Systems / methods
  • Fluorescein / chemistry
  • Fluorescein / pharmacokinetics
  • Humans
  • Hydrogen-Ion Concentration
  • Models, Chemical
  • Molecular Structure
  • Pectins / chemistry*
  • Pectins / metabolism
  • Pectins / pharmacokinetics
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / metabolism
  • Polygalacturonase / metabolism
  • Reproducibility of Results
  • Sulfhydryl Compounds / chemical synthesis*
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / pharmacology
  • Technology, Pharmaceutical / methods
  • Temperature
  • Viscosity

Substances

  • Carbodiimides
  • Pharmaceutical Preparations
  • Sulfhydryl Compounds
  • 1-ethyl-3-(3-dimethylaminoethyl)carbodiimide
  • Pectins
  • Polygalacturonase
  • Cysteine
  • Fluorescein