Synthesis of hollow polymer particles for drug delivery

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Copyright: Gu, Wenfang
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Abstract
Hollow microparticles have a range of potential applications in the area of controlled drug delivery systems as the empty core allows the encapsulation of a range of material in high concentrations. The object of this thesis is to investigate the synthesis of hollow microspheres for drug delivery systems by suspension polymerization. The hollow microspheres were subsequently modified for drug delivery purposes or to introduce bioactive functionalities. A simple process was developed to obtain hollow microspheres, utilizing an o/w suspension system with monomer droplets consisting of monomer and a solvent, which is miscible with the monomer but represents a non-solvent for the resulting polymer. Ethylene glycol dimethacrylate (EGDMA) was utilized as the building block for the majority of the studies, which were copolymerized with various other monomers to alter the properties of the hollow microspheres. The solvent butyl acetate enabled the precipitation of the polymer on the water-oil interface, therefore creating hollow spheres. Poly(EGDMA) microspheres were highly crosslinked and underwent only limited swelling. Crosslinking density was reduced by introducing methyl methacrylate (MMA) or tert-butyl methacrylate (tBuMA) as comonomer. The influences on particle size, shell thickness and core space by crosslinker, comonomers and solvent were thoroughly investigated. Hydrolysis of the poly(EGDMA-co-tBuMA) microspheres yielded pH-responsive particles, which showed different swelling depending on pH value. Bis(2-methacryloyloxyethyl) disulfide was synthesized to replace the stable crosslinker EGDMA to form degradable hollow spheres using the same suspension technique. The degradation in a reductive environment was studied using dithiothreitol (DTT) solution. Poly(EGDMA) hollow spheres were further modified using excess double bonds, which were present to a high percentage mainly on the surface, but also in the bulk of the material. Thiol-ene chemistry was employed to attach thio-glucose via electrophilic addition to result in bioactive spheres that can bind concanavalin A, a protein that adheres to glucose. Poly(EGDMA) hollow spheres could also embody a suitable reactive and stable scaffold for further reaction with malonate via Michael Addition to create a drug carrier for platinum drugs. The microspheres were of loaded with cis-dichlorodiammineplatinum (II) (CDDP) and release and anti-cancer activity were tested.
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Author(s)
Gu, Wenfang
Supervisor(s)
Stenzel, Martina
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Publication Year
2011
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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