Abstract
Flavonoids are natural organic compounds that are derivatives of diphenylpropane. This group of polyphenols can be found in multiple natural sources and they exhibit a variety of biological effects. Despite the wide array of beneficial properties, the development of drugs based on these compounds is hindered by their low bioavailability. Although the substantial body of information available on strategies to enhance the solubility and bioavailability of flavonoids, this knowledge remains fragmented. Therefore, the aim of this study was to consolidate and systematize scientific data on methods for increasing the solubility and bioavailability of flavonoid compounds without changing their initial molecular structures. Throughout the investigation, it was determined that the most prevalent methods for increasing solubility and bioavailability include co-crystallization, formation of phospholipid and inclusion complexes, and the creation of nanostructures. Although there were no pronounced differences observed in enhancing solubility, the impact of these methods on pharmacokinetic parameters was established. It was found that the production of inclusion complexes and nanostructures leads to the greatest increase in the area under the pharmacokinetic curve by an average of 4.2 and 3.7 times, respectively. The least effect was noted for phytosomes, where this parameter for the modified forms exceeded the initial value by only 1.7 times. Phospholipid complexes exhibited a longer average half-elimination time than all other modifications, achieving a 2.1-fold increase. For nanostructures and micelles, a substantial increase in maximum concentration of the active substance in blood plasma was observed, reaching an average of 5.4 times for both types of modifications. During the systematization and generalization of the data, a high level of heterogeneity in solubility assessment methods across various studies was revealed, complicating comparisons of original data obtained by different researchers. The findings of this review are crucial for researchers investigating the bioavailability of flavonoid compounds and will facilitate the selection of the most effective methods based on the desired outcomes for solubility and bioavailability.