In this thesis, I used a two-phase gas-liquid segmented microfluidic platform to synthesize drug-loaded block copolymer nanoparticles. In Chapter 2 and 3, the anti-cancer drug 7-ethyl-10-hydroxycamptothecin (SN-38) was physically encapsulated in poly(6-methyl-caprolactone-co-ε-caprolactone)-block-poly(ethylene oxide) (P(MCL-co-CL)-b-PEO) nanoparticles with various drug-to-polymer loading ratios, under different flow conditions. The effects of chemical and flow conditions on the size, morphology, drug loading efficiency, in vitro release and cytotoxicity of the nanoparticles were determined. For various loading ratios, the intermediate total flow rate (Q = 200 µL/min) produced the smallest nanoparticle sizes and pure spheres. The various nanoparticle preparation conditions showed flow-variable release rates and cytotoxicities against MCF-7 cancer cell line. Specifically, we found that release half times of SN-38 from the nanoparticles were from τ1/2 = 0.8 to 3.3 h as the total flow rate increased from Q = 50 to 200 µL/min. We also found that most conditions of SN-38 formulations generated stronger cytotoxicity than free SN-38. As well, at short and intermediate incubation time (48 and 72 h), the cytotoxic potency of microfluidic nanoparticles prepared at Q = 200 µL/min were slightly higher than nanoparticles prepared using a conventional bulk method, while potencies of microfluidic nanoparticles prepared at higher and lower flow rates were slightly lower than the bulk control. In Chapter 4, in order to pursue even higher shear rate and increased throughput, we switched the microfabrication material to silicon/glass from polydimethylsiloxane (PDMS) used in earlier chapters, maintaining the gas-liquid microfluidic reactor design. A comparison between the two microfluidic reactor materials at constant liquid flow rate showed that channel material affected both flow behaviour and the resulting nanoparticle morphologies. A new, single-phase microfluidic strategy was also proposed in order to generate high shear, in which variable high and low shear would arise from periodic changes in channel dimensions. However, issues regarding clogging of the more narrow microchannels require future work of improvements in either reactor design or the microfabrication process. / Graduate / 2019-01-12
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/7749 |
| Date | 23 January 2017 |
| Creators | Cao, Yimeng |
| Contributors | Moffitt, Matthew |
| Source Sets | University of Victoria |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
| Rights | Available to the World Wide Web |
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