Sonochemical Production of Hollow Polymer Microspheres for Responsive Delivery

  • Emily Skinner

Student thesis: Doctoral ThesisPhD


Ultrasound irradiation of a protein or polymer solution at the air:waterinterface can be used to form hollow microspheres containing an airbubble. By introducing a layer of oil and sonicating the oil:water interface,microspheres containing an oil droplet are formed. The microspheresare stabilised by disulfide crosslinking, have diameters ofbetween 1-20 mm and have a number of applications; gas filled proteinmicrospheres are used as ultrasound contrast agents and oil filledmicrospheres are being developed for delivery of lipophilic drugs.This project extends the scope of sonochemically produced microspheresto include water-in-oil emulsion filled microspheres, which facilitateencapsulation of hydrophilic species, and polymer microspheresthat release their contents in response to an external stimulus. Successfulencapsulation of a water in oil emulsion phase is demonstratedusing confocal microscopy. Release studies are reported for a numberof hydrophilic species (in vitro) including 5,6-carboxyfluorescein,5-fluorouracil and sodium chloride. Release can be triggered by sonochemicaldisruption of the microsphere shells or cleavage of thedisulfide cross links.Thiol-ene coupling reactions initiated by ultrasound irradiation arereported. In water, ultrasound initiation of thiol-ene reactions withelectron rich alkenes results in rates of reaction which compare favourablywith conventional thermal initiation. Thiol-ene crosslinking isproposed as an alternative to disulfide crosslinking to stabilise sonochemicallyproduced microspheres.Temperature responsive microspheres are produced via the sonochemicalmethod using a block copolymer of N-isopropylacrylamide andthiolated methacrylic acid, P(MASH-b-NIPAm). The block co-polymeris synthesised using reversible addition-fragmentation transfer (RAFT)polymerisation and has a lower critical solution temperature (LCST) of37 ºC. The microspheres formed from this block copolymer can be seento rupture, releasing their internal oil phase, when heated above 37 ºC.These findings provide a basis from which to develop sonochemicallyproduced polymer microspheres for responsive delivery of both hydrophilicand lipophilic species.
Date of Award22 May 2013
Original languageEnglish
Awarding Institution
  • University of Bath
SupervisorGareth Price (Supervisor)


  • ultrasound
  • microspheres
  • controlled radical polymerisation

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