Synthesis of Polymeric Nanoparticles for the Controlled Release of Hydrophobic and Hydrophillic Theraputic Compounds
| dc.contributor.author | Xu, Jiang | |
| dc.date.accessioned | 2016-09-01T14:29:23Z | |
| dc.date.available | 2016-09-01T14:29:23Z | |
| dc.date.issued | 2016-09-01 | |
| dc.date.submitted | 2016-08-22 | |
| dc.description.abstract | Polymeric nanoparticle (NP) drug carriers present a promising technology for controlled release since they are capable of improving the encapsulation efficiency and stability of the drugs inside the NPs and also able to provide effective drug levels over a longer period of time, compared to traditional therapy. However, before the NP drug delivery technology becomes a reality, important parameters of NPs like size, drug loading ability and sustained release kinetics must be well investigated and optimized in order to minimize the adverse effects of chemotherapeutic compounds and prolong the drug releasing profile in a controlled manner. In order to accomplish this objective, this thesis proposed two novel methods for synthesis of NPs as drug delivery carriers, with assistance from bulk and microfluidic technologies, for hydrophobic and hydrophilic drugs, individually. For encapsulation of hydrophobic drugs, a modified flow focusing method was developed on a glass capillary microfluidic platform. Unlike conventional microfluidic flow focusing using two miscible phases, an insoluble component (DCM) was introduced into the dispersed phase to form a partially water-miscible precursor, and a transformation phenomenon of “jet—micro droplets--nanoparticles” was firstly observed instead of the “jet—micro droplets” or “jet—nanoparticles” from traditional flow focusing. Using Doxorubicin as a drug model, size-tunable Doxorubicin-PLGA NPs (80~170 nm) were synthesized by adjusting the flow rates, polymer concentration and the volume fraction of DCM in dispersed phase with an excellent monodispersity (PDI=0.1~0.2) which was superior to those from conventional flow focusing. We also found that drug loading content increased when volume ratio of DCM/DMSO in dispersed phase increased, with a considerable mass loading ratio up to 26.3%. In addition, Doxorubicin-PLGA NPs synthesized with DCM/DMSO precursor exhibited a slower drug release profile than those synthesized with pure DMSO precursor. This modified flow focusing method can also be extended to encapsulate inorganic compounds, such as iron oxide (Fe2O3) for a combination of chemotherapy and thermo-therapy, and showed a better loading ability of Fe2O3 than conventional research using pure DMSO. This method successfully combined the advantages from previous classical drug encapsulation techniques: small particle size, ease to operation—like nanoprecipitation; monodispersity, high drug encapsulation efficiency—like emulsion-based methods, provided us a promising tool for preparing nanoparticle carriers for multiple drug loading of both organic drugs and inorganic compounds For encapsulation and release of hydrophilic drugs, a modified bulk drop-wise nanoprecipiation method was designed by separating drug and polymer into aqueous and DMSO phases, respectively. In this case, we successfully solved the problem of the poor solubility of hydrophilic drug in organic solvents, for which reason the traditional nanoprecipitation method was limited to the application of hydrophilic drug encapsulation. Monodisperse ciprofloxacin-loaded PLA (poly (D,L-lactide))-Dextran and PLGA-PEG (poly (lactide-co-glycolide)-block-poly (ethylene glycol)) NPs were prepared of a tunable size range (80~200 nm). The drug loading ability, up to 18.6% (w/w), was found having an excellent linear correlation with the original feed of the ciprofloxacin drug, which indicated that drug content encapsulated by the NPs could be precisely controlled and an in-vitro sustained release was achieved up to 95.4% in 6 days. This thesis demonstrated the design and mechanism of different drug encapsulation and release systems; and synthesis, characterization, and optimization of drug-loaded polymeric nanoparticles. Our novel drug delivery systems significantly improved the encapsulation efficiency of various therapeutic compounds and exhibited a sustained-release profile. These nano-drug-delivery systems exploited intrinsic properties of NPs for controlled release, and will not only benefit the field of nanobiomedicine, but also could be further applied to food, flavor, fragrance and cosmetics industry. | en |
| dc.identifier.uri | http://hdl.handle.net/10012/10778 | |
| dc.language.iso | en | en |
| dc.pending | false | |
| dc.publisher | University of Waterloo | en |
| dc.subject | Polymeric nanoparticles | en |
| dc.subject | controlled release | en |
| dc.subject | microfluidics | en |
| dc.subject | nanoprecipitation | en |
| dc.subject | nanotechnology | en |
| dc.title | Synthesis of Polymeric Nanoparticles for the Controlled Release of Hydrophobic and Hydrophillic Theraputic Compounds | en |
| dc.type | Doctoral Thesis | en |
| uws-etd.degree | Doctor of Philosophy | en |
| uws-etd.degree.department | Chemical Engineering | en |
| uws-etd.degree.discipline | Chemical Engineering (Nanotechnology) | en |
| uws-etd.degree.grantor | University of Waterloo | en |
| uws.contributor.advisor | Gu, Frank | |
| uws.contributor.advisor | Colin, Annie | |
| uws.contributor.affiliation1 | Faculty of Engineering | en |
| uws.peerReviewStatus | Unreviewed | en |
| uws.published.city | Waterloo | en |
| uws.published.country | Canada | en |
| uws.published.province | Ontario | en |
| uws.scholarLevel | Graduate | en |
| uws.typeOfResource | Text | en |