title: A novel, biodegradable and reversible polyelectrolyte platform for topical-colonic delivery of pentosan polysulphate.
abstract: The goal of the present work was to develop a swellable hydrogel colonic delivery system, which would maximise the availability of the therapeutic agent at a site of inflammation, especially where the water is scarce. A novel method was developed to manufacture a biodegradable and reversible polyelectrolyte complex (PEC) containing chitosan and poly acrylic-acid (PAA). The PEC was analysed using FTIR and DSC, which confirmed the formation of non-permanent swollen gel-network at an alkaline pH. Pentosan polysulphate (PPS) was incorporated in a PEC and an activated partial thromboplastin time assay was developed to measure the release of PPS from PEC. In vitro studies suggested that the release of PPS was dependent on the initial drug loading and the composition of the PEC. The gel strength of the swollen network, determined using a texture analyser, was dependent on polymer composition and the amount of PPS incorporated. Bacterial enzymes were collected from the rat caecum and colon for the digestion studies and characterised for glucosidase activity, glucuronidase activity and protein content. The digestion of the reversible polyelectrolyte complexes was measured using a dinitro salicylic acid assay and an increased release of drug was also confirmed in the presence of bacterial enzymes.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0NR, UK. hkshah99@yahoo.com
authors.forename: Hardik K
authors.initials: HK
authors.lastname: Shah
authors.forename: Jim A
authors.initials: JA
authors.lastname: Conkie
authors.forename: Robert C
authors.initials: RC
authors.lastname: Tait
authors.forename: James R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Clive G
authors.initials: CG
authors.lastname: Wilson
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000925:Anticoagulants / Q000008:administration & dosage / Q000737:chemistry; D001419:Bacteria / Q000201:enzymology*; D001777:Blood Coagulation / Q000187:drug effects; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D003106:Colon / Q000382:microbiology*; D004063:Digestion; D004337:Drug Carriers; D004339:Drug Compounding; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D005959:Glucosidases / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D010314:Partial Thromboplastin Time; D010426:Pentosan Sulfuric Polyester / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000180:Acrylic Resins; D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D004337:Drug Carriers; D005765:Gastrointestinal Agents; D020100:Hydrogels; D010426:Pentosan Sulfuric Polyester; C006903:carbopol 940; D048271:Chitosan; D005959:Glucosidases; D005966:Glucuronidase