Ultrasound irradiation of a protein or polymer solution at the air:water interface can be used to form hollow microspheres containing an air bubble. By introducing a layer of oil and sonicating the oil:water interface, microspheres containing an oil droplet are formed. The microspheres are stabilised by disulfide crosslinking, have diameters of between 1-20 mm and have a number of applications; gas filled protein microspheres are used as ultrasound contrast agents and oil filled microspheres are being developed for delivery of lipophilic drugs. This project extends the scope of sonochemically produced microspheres to include water-in-oil emulsion filled microspheres, which facilitate encapsulation of hydrophilic species, and polymer microspheres that release their contents in response to an external stimulus. Successful encapsulation of a water in oil emulsion phase is demonstrated using confocal microscopy. Release studies are reported for a number of hydrophilic species (in vitro) including 5,6-carboxyfluorescein, 5-fluorouracil and sodium chloride. Release can be triggered by sonochemical disruption of the microsphere shells or cleavage of the disulfide cross links. Thiol-ene coupling reactions initiated by ultrasound irradiation are reported. In water, ultrasound initiation of thiol-ene reactions with electron rich alkenes results in rates of reaction which compare favourably with conventional thermal initiation. Thiol-ene crosslinking is proposed as an alternative to disulfide crosslinking to stabilise sonochemically produced microspheres. Temperature responsive microspheres are produced via the sonochemical method using a block copolymer of N-isopropylacrylamide and thiolated methacrylic acid, P(MASH-b-NIPAm). The block co-polymer is synthesised using reversible addition-fragmentation transfer (RAFT) polymerisation and has a lower critical solution temperature (LCST) of 37 ºC. The microspheres formed from this block copolymer can be seen to rupture, releasing their internal oil phase, when heated above 37 ºC. These findings provide a basis from which to develop sonochemically produced polymer microspheres for responsive delivery of both hydrophilic and lipophilic species.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:577749 |
| Date | January 2013 |
| Creators | Skinner, Emily K. |
| Contributors | Price, Gareth |
| Publisher | University of Bath |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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