DEVELOPMENT OF ALGINATE NANOSPHERES AS A PROTEIN DELIVERY DEVICE FOR CARTILAGE TISSUE ENGINEERING
Yasmin, Farhana 1990-
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Delivery of bioactive proteins is a valuable strategy in cartilage tissue engineering (CTE) because of their ability to regulate the gene expression and extracellular matrix (ECM) production of engineered cartilage. This, however, has been challenged by the nature of bioactive proteins including their instability, poor tissue penetration ability, short half-life and a relatively high price. Development of nanospheres as a protein delivery device should solve these issues by promoting the temporal and spatial presentation of such bioactive proteins in a defined target for the enhanced half-life time and effectiveness. Among various polymer-based micro/nanospheres, alginate micro/nanospheres have been widely used as a protein delivery device because of their mild and easy protein encapsulation process, inert nature, non-toxicity and biocompatibility. However, one of the major limitations of using alginate as a protein delivery device is its high initial burst release due to its high porosity and instability if exposed in a higher pH release media. To address these issues, this study aimed to develop the protein loaded alginate nanospheres as a delivery device with a reduced initial burst release. The hypothesis was, “Increasing the alginate concentration, cross-linking time or drying time reduces the initial burst release independently of associated changes to the size and number of nanospheres.” Bovine Serum Albumin (BSA) was used as a model protein in this study to evaluate the performance of alginate nanospheres as a protein delivery device, while protein loaded alginate nanospheres were prepared via a combination of water-in-oil emulsification and external gelation method. The process parameters tested to reduce the initial burst release include, alginate concentration, cross-linking time and drying time. The effects of these process parameters on the nanosphere size and distribution pattern, relative number of microspheres, initial burst release, protein release kinetics and encapsulation efficiency (EE%) were investigated. Also, if the change in size and relative number of nanospheres by varying these process parameters affected the initial burst release was investigated. It has been illustrated that by properly increasing the alginate concentration, cross-linking time and drying time it was possible to reduce initial burst release by 13%, and among various process parameters only the alginate concentration showed a significant effect on the initial burst release, when considered alone. Also, it was confirmed that during determination of the effect of various process parameters the relative number of nanospheres significantly affected the initial burst release. Taken together, this study demonstrates that regulating various process parameters is a mean to reduce initial burst release of alginate nanospheres, urging more studies on alginate nanospheres for their potential application in CTE.
DegreeMaster of Science (M.Sc.)
SupervisorChen, Daniel; Eames, Brian
CommitteeZhu, Ning; Boughner, Julia; Wasan, Ellen
Copyright DateNovember 2018