Theses (MSc. Medical and Health Sciences)

Miktoarm star polymers have increasingly attracted scientists’ attention due to their intriguing properties which can be tailored by varying their polymer arms. In this study, a series of miktoarm star copolymers, abbreviated as PLGA-AAA-mPEG2, with different PLGA arm molecular weights (4600 g/mol, 7000-17000 g/mol and 43400 g/mol) and methoxypoly(ethylene glycol) (mPEG) arm (2000 g/mol), were synthesised via a four-step reaction using carbodiimide chemistry and a low steric hindrance trifunctional linker aminoadipic acid (AAA). The structures of these miktoarm star polymers were characterised and confirmed with nuclear magnetic resonance (1H NMR) and fourier transform infrared (FTIR) techniques. Gel permeation chromatography (GPC) and differential scanning calorimetry (DSC) were used to measure molecular weights and thermal properties, respectively. Nanoparticle formulation results showed that the miktoarm star polymers PLGA17000- AAA-mPEG2 and PLGA43400-AAA-mPEG2 could form stable nanoparticles by emulsion solvent evaporation method using 1% (w/v %) PVA as aqueous phase, 1:10 drug to miktoarm star polymer ratio and 3:1 trehalose to miktoarm star polymer ratio. In contrast, PLGA4600-AAA-mPEG2 was self-assembled into stable nanomicelles by a dialysis method in which DMSO was found to be the best solvent. Model drug ibuprofen was successfully loaded into the corresponding nanoparticles and nanomicelles that had good drug loading, high encapsulation efficiency and narrow size distribution. Other critical features of nanoparticles and nanomicelles studied included particle size, zeta potential and surface morphology. The mean particle size increased with increasing miktoarm star polymer molecular weight: PLGA4600-AAAmPEG2 (37.28 ± 1.03 nm) followed by PLGA17000-AAA-mPEG2 (103.29 ± 1.59 nm) iv and PLGA43400-AAA-mPEG2 (151.46 ± 0.86 nm). Zeta potential of PLGA17000- AAA-mPEG2 (-22.43 ± 1.43 mV) was higher in magnitude, indicative of higher stability, than those of PLGA43400-AAA-mPEG2 nanoparticles (-11.24 ± 0.44 mV) and PLGA4600-AAA-mPEG2 nanomicelles (-6.02 ± 0.39 mV). Drug loading (DL) and encapsulation efficiency (EE) of PLGA17000-AAA-mPEG2 nanoparticles (DL: 6.96 ± 1.31 %; EE: 76.53 ± 14.34 %) were higher than those of PLGA43400-AAA-mPEG2 nanoparticles (DL: 2.92 ± 0.34 %, EE: 32.04 ± 3.71 %) and PLGA4600-AAA-mPEG2 nanomicelles (DL: 5.39 ± 1.33 %, EE: 59.26 ± 14.58 %). In vitro release of ibuprofen over 7 days from PLGA43400-AAA-mPEG2 nanoparticles (61.65 ± 3.04 %) was higher than those of PLGA4600-AAA-mPEG2 nanomicelles (26.93 ± 1.49 %) and PLGA17000-AAA-mPEG2 nanoparticles (10.57 ± 0.29 %) while all showed controlled release characteristics. In addition, TEM images had shown that the shape of nanoparticles and nanomicelles were almost spherical. The findings suggest that the novel miktoarm star polymers PLGA43400-AAA-mPEG2 and PLGA17000-AAAmPEG2 and their nanoparticles, and PLGA4600-AAA-mPEG2 and its nanomicelles have a great potential as a nanocarrier for controlled delivery of hydrophobic drugs.