Browsing by Author "Ball, Lauren Elaine"

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    Synthesis and characterisation of hairy poly(lactic acid) nanoparticles
    (Stellenbosch : Stellenbosch University, 2021-03) Ball, Lauren Elaine; Klumperman, Bert; Pfukwa, Rueben; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.
    ENGLISH ABSTRACT: The encapsulation of active pharmaceutical ingredients (APIs) within drug delivery systems Such as polymeric nanoparticles (PNPs) vastly improves the therapeutic efficiency of the incorporated APIs. PNPs synthesised using block copolymers, constituting a hydrophilic and hydrophobic block segment, such as poly(lactic acid)-block-poly(ethylene glycol) (PLA-b-PEG), are efficient drug delivery systems. The hydrophobic block copolymer segment is incorporated into the core of the PNP and the hydrophilic block segment makes up the hairy corona of the PNP, aiding in stabilisation of the nanocarriers against aggregation in solution. Poly(N-vinyl pyrrolidone) (PVP) and poly(styrene-alt-maleic acid) (SMA) are attractive alternatives for the hydrophilic corona of PLA based nanoparticles. Unlike PEG, PVP is stable against lyophilisation, whilst SMA provides ample opportunity for post polymerisation functionalisation via the maleic anhydride (MAnh) units of the parent poly(styrene-alt-maleic anhydride) (SMAnh) copolymer. A method for the synthesis of PLA-b-PVP and PLA-b-SMA, via a combination of ring opening polymerisation (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerisation, is presented. Two different PLA macro chain transfer agents (CTAs) were successfully synthesised via ROP and subsequent post-polymerisation chain end functionalisation. Both PLA macro-CTAs were successfully chain extended to yield PLA-b-PVP and PLA-b-SMA copolymers, which were fully characterised via ATR-FTIR spectroscopy, 1H NMR spectroscopy, size exclusion chromatography (SEC) and DOSY NMR spectroscopy. The xanthate mediated RAFT polymerisation of PVP, using a thermal initiator, at elevated temperatures can lead to the occurrence of side reactions. One such side reaction is the cleavage of the xanthate chain end due to its thermal lability, leading to loss of control over the RAFT polymerisation. An alternative method of PVP synthesis was therefore introduced which made use of amine-peroxide redox polymerisation (APRP) as an alternative method for radical production. A combination of two different tertiary amines and benzoyl peroxide (BPO) was used as the redox initiating pair. The first amine utilised was 4-(dimethylamino)pyridine (DMAP) and the second was N-(4-methoxyphenyl)pyrrolidine (MPP). MPP/BPO allowed for faster rates of polymerisation to be realised compared to DMAP/BPO. The APRP mediated RAFT synthesis of PVP was also investigated and allowed for some control over the polymerisation to be achieved. Each block copolymer underwent nanoprecipitation to yield monodisperse nanoparticles (NPs) ranging in size between 60 and 220 nm. PLA-b-PVP NP diameters could be tuned by variation of the organic solvent utilised during nanoprecipitation and PLA-b-SMA NP diameters could be tuned via variation of the block copolymer concentration. The lipophilic fluorescent dye DiI could be encapsulated within PLA-b-PVP and PLA-b-SMA NPs successfully and these fluorescent NPs were used in a preliminary cell uptake study. Both hairy PVP and SMA NPs were taken up successfully by H9c2 cells.