Sonochemical Production of Hollow Polymer Microspheres for Responsive Delivery

Abstract

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 Award	22 May 2013
Original language	English
Awarding Institution	University of Bath
Supervisor	Gareth Price (Supervisor)