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Title: Modulating docetaxel encapsulation and release from branched vinyl copolymer nanoparticles formed via co-nanoprecipitation
Author: Flynn, Sean
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2019
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The acute toxicity and inherent low water solubility of many chemotherapeutics often prevent such drugs from achieving the optimal therapeutic effect in a clinical setting. Branched vinyl copolymer nanoparticles have been investigated as potential drug delivery vehicles for the controlled release of docetaxel, a commercially available hydrophobic anti-cancer drug. Branched vinyl copolymer nanoparticles were produced via co-nanoprecipitation; this relatively new nanoformulation technique involved the simultaneous nanoprecipitation of high molecular weight, hydrophobic branched copolymers with their corresponding amphiphilic AB block copolymers, through a rapid manipulation of their solvent environment. This approach was used to entrap docetaxel molecules within the hydrophobic cores of branched vinyl copolymer nanoparticles during the co-nanoprecipitation process. A comprehensive study was undertaken to expand the scope of branching vinyl copolymer nanoparticles that can be produced via co-nanoprecipitation, beyond the limited number of nanomaterials that have been reported to date. This involved co-nanoprecipitation of a large number of hydrophobic and amphiphilic polymers which possessed a wide range of different chemical and physical properties. This required the development of an unlikely synthetic approach, copper-catalysed reversible-deactivation radical polymerisation in anhydrous alcoholic media, for the development of novel hydrophobic polymeric materials. Fundamental studies were conducted to understand the experimental factors which influence nanoparticle formation during co-nanoprecipitation and, where possible, these factors were used as leavers to influence nanoparticle characteristics. Promising branched vinyl copolymer nanoparticle candidates were taken forward to drug encapsulation and release studies. This involved the use of radiometric techniques to quantify the encapsulation and release of docetaxel from branched vinyl copolymer nanoparticles. Docetaxel loadings of up to 25 weight % of the total nanoparticle mass and encapsulation efficiencies of up to 97 % were achieved during co-nanoprecipitation. The properties of the polymers used to construct branched vinyl copolymer nanoparticles also had a significant impact on docetaxel release. The impact of nanoparticle properties, including core polarity and viscosity, on the levels of docetaxel entrapment during co-nanoprecipitation and the rate of docetaxel release will be presented. The suitability of leading nanoparticle candidates as prospective drug nanocarriers in vivo will be discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral