Facile microfluidic production of polyethylene glycol (PEG) - based microgel particles in a novel microfluidic device and their applications

Promising hydrophilic and photo-polymerisable hydrogel, Poly (ethylene glycol) diacrylate (PEGDA), opens up many exciting opportunities for pharmaceutical, biomedical and environmental applications. Microfluidics, as a technology involving a multidisciplinary approach, utilises the precise control and manipulation of fluids at the microscale. Thus, the combination of hydrogel and microfluidics is powerful, and the possibilities seem limitless. This thesis is concerned with a facile microfluidic production of PEGDA microgel particles in a novel Lego®-inspired glass capillary microfluidic device and the exploration of their various potential applications. The development of an efficient microfluidic platform for the generation of emulsion droplets and in-situ encapsulation was accomplished, along with the achievement of novel and easily reproducible PEGDA hydrogels synthesis strategies. In addition, the modification and functionalisation of hydrogel with tunable properties and structure for the aimed applications are crucial ideas for designing hydrogels. This thesis presents research on the development and application of photopolymerised PEGDA hydrogel microparticles based on microfluidic production in five stages.

In stage one, the production of the template pure PEGDA particles lays the foundation for future research on the modification of hydrogel particles. Monodispersed PEGDA microgels were produced by modular droplet microfluidics using the dispersed phase with 49–99 wt% PEGDA prepolymer, 1 wt% Darocur 2959, and 0–50 wt% water, while the continuous phase was 3.5 wt% silicone-based surfactant dissolved in silicone oil. Pure PEGDA droplets were fully cured within 60 s at the UV light intensity of 75 mW·cm-2, and even were polymerised through a cell harmless strategy using blue light with Eosin ‘Y’ as a photo-initiator. The droplets with higher water content required more time for curing. Due to oxygen inhibition, the polymerisation started in the droplet centre and advanced towards the edge, leading to a temporary solid core/liquid shell morphology, confirmed by tracking the Brownian motion of fluorescent latex nanoparticles within a droplet. A volumetric shrinkage during polymerisation was 1–4% for pure PEGDA droplets and 20– 32% for the droplets containing 10–40 wt% water. The particle volume increased by 36–50% after swelling in deionised water. The surface smoothness and sphericity of the particles decreased with increasing water content in the dispersed phase. The porosity of swollen particles was controlled from 29.7% to 41.6% by changing the water content in the dispersed phase from 10 wt% to 40 wt%.

In stage two, the aim was to explore feasible methods to achieve the controlled release of drugs, molecularly dispersed or present as nanoparticles, in PEGDA hydrogels and potentially apply them to drug delivery systems as drug hydrogel-based carriers. Monodispersed PEGDA hydrogel microspheres as microcarriers were produced using a Lego®-inspired microfluidic device. Shrinkage/swelling behaviour was investigated during droplet curing and particle transfer from oil to an aqueous phase and during hydrolysis in alkaline media. The swelling characteristics was investigated using pure PEGDA particles and PEGDA particles loaded with graphene nanoplatelets, titanium (IV) oxide nanoparticles and polystyrene nanoparticles in deionised water and 0.1M NaOH. Controlled release studies were conducted using fluorescent polystyrene nanoparticles and fluorescent calcein dye as mock actives. Polystyrene nanoparticles, entrapped in the polymer matrix were released at the rate that was dependant on the pH of the release medium. Calcein release was affected by introducing graphene nanoplatelets and titanium (IV) oxide nanoparticles into the polymer network. Release experiments were evaluated and predicted by applying mathematical models based on Fick’s second law of diffusion and comparing diffusion coefficients under various release conditions.

In stage three, metal-PEGDA hybrid beads were developed to be used as catalysts and photocatalysts for the chemical reactions of degradation of organic pollutants. Two types of catalytic PEGDA beads were produced: Ag-coated beads and TiO2-loaded beads. For producing catalytic Ag-PEGDA beads, the monodisperse PEGDA microgel particles were obtained and used as microcarriers for an in-situ synthesis and stabilisation of silver nanoparticles using silver nitrate as a metal precursor and sodium borohydride as a reducing agent. Ag-PEGDA hybrid beads were applied as an efficient catalyst for the reduction of 4-nitrophenol (4-NP) into 4-aminophenol (4-AP) in the presence of sodium borohydride at room temperature. The progress of the reaction was monitored by UV- Visible spectrophotometry by measuring the decline of absorbance peak at 400 nm. 4-NP was successfully converted to 4-AP and the reaction followed pseudo-first-order kinetics. Ag-PEGDA system was also found as an effective recyclable catalyst for room-temperature degradation of methylene blue in the presence of NaBH4. Composite Ag-PEGDA microgel beads have the potential to be used as an eco-friendly and easily recoverable catalyst for the transformation of other organic pollutants into useful chemicals. Additionally, the photocatalytic TiO2-loaded hydrogel beads were produced through in-situ encapsulation of TiO2 nanoparticles into a prepolymer solution. TiO2-PEGDA hybrid system was used as an adsorbent and photocatalyst for the removal of methylene blue (MB) from an aqueous medium. Kinetics parameters of adsorption and photocatalytic degradation were evaluated using pseudo-first and pseudo-second-order models. Processes of adsorption and photocatalysis were explored on the basis of adsorption data and degradation data, respectively. It has been found that TiO2-PEGDA system has excellent recyclability towards the degradation of methylene blue. TiO2-PEGDA system can be used for the removal of other toxic dyes from industrial wastewater.

In stage four, PEGDA microgels were chemically modified by the incorporation of a positively charged comonomer [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAETAC), and macroporosity was created by adding a non-crosslinkable PEG in the monomer mixture. The positively charged porous, P(EGDA-co-MAETAC), microgel particles were produced by microfluidic emulsification of monomer mixture using the Lego®-inspired glass capillary device and subsequent UV polymerisation of monomer mixture within droplets. The charged, porous beads were used as highly efficient adsorbents for the removal of negatively charged organic molecules, such as Congo red (CR) and negatively charged ions, such as Cr (VI), from aqueous media. The Congo red sorption mechanism onto the positively charged PEGDA microspheres obeyed the Langmuir and Freundlich sorption isotherm models. The modified hydrogel adsorbents displayed excellent adsorption capability towards anions combined with increased repulsion of cations.

The research work presented in this thesis demonstrates the feasibility of microfluidically fabricated PEGDA-based hydrogel microparticles to be used as excipients in drug delivery systems, adsorbents of organic pollutants, catalysts and photocatalysts. It provided reliable evidence and good signs for future application directions to explore.