title: Unusual behaviour induced by phase separation in hydrogel microspheres.
abstract: Hydrogel microspheres with the capability to interact with charged species such as various drugs by ion-exchange processes are useful in a variety of biomedical applications. Such systems have been developed to allow active loading of the microsphere with chemotherapeutic agents in the hospital pharmacy for subsequent locoregional therapy of tumours in the liver by drug-eluting bead chemoembolization (DEB-TACE). A variety of microspherical embolisation systems have been described, all based upon hydrogels bearing anionic functionalities to allow interaction with cationically charged drugs. We have recently prepared a series of microspheres bearing cationic functionality and have observed some unusual behaviour induced by phase-separation that occurs during the synthesis of the microspheres. The phase-separation results in the core of the microsphere being enriched in cationic polymer component compared to the outer polyvinyl alcohol (PVA)-based phase. For certain formulations, subsequent swelling in water results in the PVA-rich skins separating from the charged cores. Ion-exchange interactions with model compounds bearing multi-anionic groups create differential contraction of the charged core relative to the skin, resulting in an unusual "golf-ball" appearance to the surface of the microspheres.
  
  
  
  The authors believe that the unusual behaviour of the microspheres reported in this paper is the first observation of its kind resulting from phase-separation during synthesis. This could have novel applications in drug delivery for systems that can respond by shedding their skin or altering the surface area to volume ratio upon loading a drug.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton BN2 4GJ, UK; Biocompatibles UK Ltd, Farnham Business Park, Weydon Lane, Farnham, Surrey GU9 8QL, UK.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Heaysman
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton BN2 4GJ, UK.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Philips
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton BN2 4GJ, UK.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Lloyd
authors.affiliation: Biocompatibles UK Ltd, Farnham Business Park, Weydon Lane, Farnham, Surrey GU9 8QL, UK. Electronic address: andrew.lewis@biocompatibles.com.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D002412:Cations / Q000737:chemistry; D016461:Chemoembolization, Therapeutic / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000302:isolation & purification; D066298:In Vitro Techniques; D007474:Ion Exchange; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D044367:Phase Transition; D011142:Polyvinyl Alcohol / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D002412:Cations; D003692:Delayed-Action Preparations; D020100:Hydrogels; D000644:Quaternary Ammonium Compounds; D011142:Polyvinyl Alcohol; C523720:(3-acrylamidopropyl)trimethylammonium chloride
keywords: Hydrogel microspheres; Ion-exchange; Phase-separation