Drug delivery systems for enhanced neuroprotective effects of polyphenols: Current status and challenges

Plants are a natural and diverse source of numerous bioactive compounds, including flavonoids, carotenoids, phytoestrogens, and alkaloids. These bioactive compounds have been used in complementary and alternative medicine worldwide. The naturally occurring polyphenols present abundantly in fruits, vegetables, and cereals are phytochemicals with various biological activities. Purified polyphenols can be used as potential drugs to modulate cell growth, cell survival, oxidative stress, and inflammation in several disease conditions, such as cardiovascular diseases, neurological disorders, metabolic syndrome, and cancer. Recent studies in animal models have shown that some polyphenols have beneficial effects on brain health. At the cellular level, polyphenols can promote neurogenesis and synaptogenesis, thus, providing neuroprotection and promoting neuro-regeneration. The neuroprotective effects of polyphenols have been observed in vitro models as well as in animal models of diseases . Although polyphenols are promising therapeutic candidates that can be developed as drugs for treating neurological disorders, there are caveats that need to be addressed. Most importantly, polyphenols have limited water solubility and high susceptibility to heat, light, and extreme pH conditions all of which negatively affects their bioavailability, thereby limiting their application as pharmacological agents. To address this, researchers have tried to develop diverse drug delivery systems that can be used for effective delivery of polyphenols in animal models of neurodegenerative diseases. These drug delivery systems work by increasing the absorption, bioactivity, and stability of polyphenols. Studies have shown that coupling polyphenols with various drug delivery systems can reduce the therapeutic dose, enhance their stability, and enhance the therapeutic effect through various mechanisms. This review focuses on the neuroprotective effects of polyphenols and discusses current challenges and limitations of various drug delivery systems developed for increasing the neuroprotective efficacy of these bioactive molecules. Polyphenols are phytochemicals of therapeutic importance since they possess bioactive properties. However, the therapeutic applications of polyphenols are currently limited due to their poor aqueous solubility, low stability and low bioavailability. To address these issues, novel drug delivery systems based on biodegradable and biocompatible materials have been developed for targeted and efficient polyphenol delivery.