title: Design of a pectin-based microparticle formulation using zinc ions as the cross-linking agent and glutaraldehyde as the hardening agent for colonic-specific delivery of resveratrol: in vitro and in vivo evaluations.
abstract: The aim of this study was to develop a colon-specific microparticle formulation based on pectin. Resveratrol was used as a model drug due to its potential therapeutic efficacy on colitis and colon cancer. Microparticles were produced by cross-linking pectin molecules with zinc ions and with glutaraldehyde as hardening agent for pectins. Different microparticles were prepared by varying the formulation variables. Effect of these formulation variables were investigated on particle shape and size, moisture content and weight-loss during drying, encapsulation efficiency, swelling-erosion ratio, and drug release pattern of the formulated microparticles. Formulation conditions were optimized based on the in vitro drug release study. Morphology, Fourier transform infrared spectroscopy, stability, and in vivo pharmacokinetic study of the microparticles prepared at the optimized formulation conditions were performed. Microparticles were spherical with <1 mm diameter and encapsulation efficiencies of >94%. The glutaraldehyde-modified microparticles prepared at optimized formulation conditions revealed colon specific in vitro and in vivo drug release. Plasma appearance of drug was delayed for 4-5 h after their administration directly into stomach, but displayed comparable area under the curve to other controls in the experiment, indicating the potential of the developed formulation as a colon-specific drug delivery system.
authors.affiliation: Department of Pharmacy, National University of Singapore.
authors.forename: Surajit
authors.initials: S
authors.lastname: Das
authors.forename: Ka-Yun
authors.initials: KY
authors.lastname: Ng
authors.forename: Paul C
authors.initials: PC
authors.lastname: Ho
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D015195:Drug Design; D004355:Drug Stability; D005976:Glutaral / Q000737:chemistry*; D008297:Male; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D010368:Pectins / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013267:Stilbenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D003432:Cross-Linking Reagents; D004337:Drug Carriers; D013267:Stilbenes; D010368:Pectins; D000077185:Resveratrol; D005976:Glutaral