Delivery of a desired ‘active’ compound (for example, starch (as an energy substrate)) to the gastrointestinal (GI) tract is most easily achieved by oral administration. Unfortunately, the efficacy of most actives is greatly reduced due to the aggressive nature of digestive enzymes and processes which occur in this environment. A commonly applied strategy to prevent deactivation of the active prior to absorption at the target site is to encapsulate the active in another ‘sacrificial’ or non-degradable polymer matrix. Traditionally, the active and matrix is processed into a microparticle format for easy oral delivery (dispersed in a liquid or paste). However, established encapsulation methods which rely on bulk-phase processing to produce these microparticles (e.g. emulsification) are far from ideal as they lack control over the final microparticle size, size distribution, composition and shape. The lack of control in the physical properties of the resultant microparticles in turn results in an inherent lack of control over the kinetics of release of the active at the target site. In contrast, recent advances in microfluidic device fabrication and methodology development have firmly proven that these new generation devices can produce monodisperse droplets and microparticles in a continuous, controllable and predictable manner. Their potential as a processing tool for the production of highly tailored microparticles for targeted delivery, however, remains to be fully explored. Both the physical and chemical (physicochemical) properties of microparticles made from a single polymer system may be altered by the deposition of one or more additional polymer layers onto the microparticle surface (for example, alternating layers of oppositely charged polyelectrolytes to produce core-shell like particles), and this method has proven to be favorable with regards to retarding the release of active compounds. However, this addition of alternate layers of oppositely charged polyelectrolytes (so called Layer-by-Layer (LbL) deposition or assembly) does increase the number of processing steps the particles must undergo prior to storage or delivery. Further, the overall effectiveness of this additional processing is still highly dependent on the properties of the original (core) microparticles. In this thesis, a microfluidic technique was developed to encapsulate starch granules in alginate-based microparticles. Using this continuous technique, the size of the microparticles produced were shown to be monodisperse and reproducible. The developed microfluidic device included a drop formation section, followed by a gelation region and a transfer section, where the particles made on-chip are transferred from the carrier oil phase to an aqueous phase prior to collection. The microparticles collected from this microfluidic device were found to be stable for several weeks and in stark contrast to particles produced via a standard bulk emulsification routes, no aggregation was observed over this time frame. The release profile of glucose (as a result of starch hydrolysation) from microparticles produced using both a standard bulk emulsification method and the developed microfluidic-based method were compared. It was found that the monodisperse particles produced using the microfluidic method showed significantly more retardation to release compared to the glucose release profile from bulk-processed particles. This retardation effect was more pronounced when a thin layer of an oppositely charged polyelectrolyte (chitosan) was adsorbed onto the negatively charged surface (alginate is an anionic polyelectrolyte) of the microfluidic-processed microparticle. The microfluidic device developed within this thesis and the resulting tailored microparticles thus show significant potential with regards to offering a new generation of microparticle delivery systems with highly deterministic delivery over extended lifetimes.
| Identifer | oai:union.ndltd.org:ADTP/287454 |
| Creators | Edeline Wong |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
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