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Using supercritical CO₂-based nanomization technology to improve the water solubility and bioavailability of soy isoflavones

Authors Xu, Jinjie
Issue Date 2010
Summary Oral administration is the most preferred route of drug intake. But it is not suitable for many drugs as they have poor bioavailability. Such a drug is genistein which is the major component of soy isoflavones and exhibits multiple health benefits including anti-cancer, anti-cardiovascular diseases, and reduction of menopausal symptoms. In addition to having low water solubility, it is quickly degraded during first pass-metabolism. Two approaches were employed in this study to improve the solubility and bioavailability of genistein. The first one is to use precipitation with compressed antisolvent (PCA) process to generate genistein nanoparticles. The second one is to utilize supercritical fluid extraction of emulsion (SFEE) process to encapsulate genistein with PLGA polymer. In the PCA process, the impact of various process parameters on particle formation was evaluated. Among the three parameters-pressure of precipitation, concentration of drug solution, and feed rate ratio of CO2/drug solution, we found that the pressure was the most important parameter that could greatly affect the particle size and morphology. Under the optimized operating conditions, the width of genistein particles was reduced from more than 10 μm to 200-250 nm. The 24-hour pharmacokinetic study performed in rats showed that the plasma concentration of nanomized genistein was 2.6 fold higher than that of the unprocessed genistein. This result demonstrated the possibility of using PCA process to improve the bioavailability of water insoluble compounds. In the second part of the project, genistein was successfully encapsulated with biodegradable polymer PLGA using the SFEE process. The results of in vitro drug release study showed that PLGA-encapsulated genistein displayed a controlled release profile compared to the original genistein indicating this encapsulation process may achieve a prolonged drug delivery effect in vivo.
Note Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2010
Language English
Format Thesis
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