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Title: Novel amphiphilic branched copolymer nanoparticles as candidates for drug delivery
Author: Slater, Rebecca
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2013
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The methanolic atom transfer radical polymerisation (ATRP) of 2-hydroxypropyl methacrylate (HPMA) to controllably form the hydrophobic polymer p(HPMA) using a one-pot methodology at ambient temperature has been demonstrated, where polymerisations were shown to reach >99 % conversion. By simple variation of initiator:monomer feed ratio, polymers of varying chain length were synthesised. Using identical polymerisation conditions, addition of a small amount of ethylene glycol dimethacrylate (EGDMA) divinyl brancher resulted in the generation of high molecular weight branched copolymers without any modification of reaction kinetics. This approach was extended to include the first synthesis of linear and branched amphiphilic A-B block copolymers using polyethylene oxide (PEG) macroinitiators without loss of the ATRP controlled polymerisation. A series of systematically varying copolymers, containing variation in PEG length and/or variation in p(HPMA) primary chain length, have been synthesised to allow direct comparison of the impact of architectural variation on polymer properties. Nanopreciptation approaches were investigated for the linear and branched copolymers and extremely stable hydrophobic nanoparticles were produced using copolymers with branched architecture. Moreover, it has been shown that nanoparticle z-average diameter can be controlled using extremely facile methods. The loading capacity of amphiphilic branched A-B block copolymer nanoparticles with various guest-molecules has been systematically investigated. The world leading HIV/AIDS antiretroviral drug Lopinavir (LPV) was used in a preliminary loading screen and shown to produce candidate LPV/drug nanocarrier options for future studies and optimisation.
Supervisor: Rannard, Steve; Weaver, Jon Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD Chemistry