title: Delivery of dermatan sulfate from polyelectrolyte complex-containing alginate composite microspheres for tissue regeneration.
abstract: Dermatan sulfate (DS) is a glycosaminoglycan (GAG) with a great potential as a new therapeutic agent in tissue engineering. The aim of the present study was to investigate the formation of polyelectrolyte complexes (PECs) between chitosan and dermatan sulfate (CS/DS) and delivery of DS from PEC-containing alginate/chitosan/dermatan sulfate (Alg/CS/DS) microspheres for application in tissue regeneration. The CS/DS complexes were initially formed at different conditions including varying CS/DS ratio (positive/negative charge ratio), buffer, and pH. The obtained CS/DS complexes exhibited stronger electrostatic interaction, smaller complex size, and more stable colloidal structure when chitosan was in large excess (CS/DS 3:1) and prepared at pH 3.5 as compared to pH 5 using acetate buffer. The CS/DS complexes were subsequently incorporated into an alginate matrix by spray drying to form Alg/CS/DS composite microspheres with a DS encapsulation efficiency of 90-95%. The excessive CS induced a higher level of sustained DS release into Tris buffer (pH 7.4) from the microspheres formulated at pH 3.5; however, the amount of CS did not have a significant effect on the release from the microspheres formulated at pH 5. Significant cell proliferation was stimulated by the DS released from the microspheres in vitro. The present results provide a promising drug delivery strategy using PECs for sustained release of DS from microspheres intended for site-specific drug delivery and ultimately for use in tissue engineering.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100, Copenhagen, Denmark.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Wen
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Grøndahl
authors.forename: Monica R
authors.initials: MR
authors.lastname: Gallego
authors.forename: Lene
authors.initials: L
authors.lastname: Jorgensen
authors.forename: Eva H
authors.initials: EH
authors.lastname: Møller
authors.forename: Hanne M
authors.initials: HM
authors.lastname: Nielsen
mesh_terms: D000464:Alginates / Q000008:administration & dosage*; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage; D049109:Cell Proliferation; D002478:Cells, Cultured; D048271:Chitosan / Q000008:administration & dosage*; D003871:Dermatan Sulfate / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004573:Electrolytes / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008863:Microspheres; D012038:Regeneration / Q000187:drug effects*; D023822:Tissue Engineering
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D004573:Electrolytes; D003871:Dermatan Sulfate; D048271:Chitosan