Modern Nanocarriers as a Factor in Increasing the Bioavailability and Pharmacological Activity of Flavonoids

Abstract

This review is devoted to modern systems of nanocarriers that ensure the targeted delivery of flavonoids to various organs and systems. Flavonoids have wide range of effects on the human body due to their antioxidant, anti-inflammatory, antitumor, antimicrobial, antiplatelet and other types of activity. However, the low bioavailability of flavonoids significantly limits their practical application. To overcome this disadvantage, serious efforts have been made in recent years to develop nanoscale carriers for flavonoids. This is particularly important in view of the known antitumor effect of these compounds, which allows them to target tumor cells without affecting surrounding healthy tissues. Nanocarriers provide increased penetration of biologicals into specific organs in combination with controlled and prolonged release, which markedly improves their effectiveness. This review summarizes data on the use of phytosomes, lipid-based nanoparticles, as well as polymeric and inorganic nanoparticles; their advantages and drawbacks are analyzed; the prospect of their use is discussed that opens new possibilities for the clinical application of flavonoids.

Introduction

Flavonoids are becoming more interesting as evidence accumulates about the beneficial effect of foods containing these compounds on human health. It is well known that flavonoids have antioxidant, anti-inflammaroty, anticarcinogenic, neuroprotective, antidiabetic, antimicrobial, and antitrombotic activity, and their application facilitates the course of various diseases [1–5]. This is of special importance due to the high availability and relative low cost of dietary flavonoids. However, it should be noted that flavonoid aglycons or polyphenol-rich extracts have mostly been studied in vitro, which raises two main concerns. First, in vivo, target organs in the body never come into direct contact with flavonoid aglycones, but only with their metabolites or conjugated forms. Second, the aglycone concentrations used in in vitro experiments are practically never achieved in the body [6, 7]. Moreover, with rare exceptions, native flavonoids (aglycones) cannot be detected in the blood [6–9], hence, there is no direct correlation between in vitro and in vivo experiments, and out-of-body reslts should be treated with caution.

The above problem, which often negates the therapeutic effectiveness of flavonoids, is mainly due to the low bioavailability of these compounds, i.e., only a small portion of the administered drug can reach the systemic circulation and target organs. The bioavailability of dietary polyphenols, like most other plant compounds, depends on numerous physicochemical and pharmacokinetic factors, including the chemical structure of representatives of a particular subclass of flavonoids, their polarity, molecular mass, plant matrix, sensitivity to pH and gastrointestinal enzymes, and degree of absorption in the small and large intestines. After absorption, lipophilic aglycones undergo metabolic transformation in the small intestine, liver, and colon. Conjugated products entering the systemic circulation after methylation, sulfation and glucuronization of flavonoids are devoid of the pronounced biological activity characteristic of aglycones in vitro [10, 11]. As an example, the blood serum of healthy people, who received 240 mg of flavonolignane silybin, contained only 0.18–0.62 μg/mL of this compound, and in bile it ranged 11–14 μg/mL [12].

Similar problems arise when it is necessary to overcome the skin barrier with topical application of flavonoids [13–15]. In this regard, increase in the bioavailability of flavonoids becomes a fundamentally important factor in enhancing their biological action. This problem is most relevant in oncological practice, where flavonoids, due to their anticarcinogenic activity, are becoming more widespread [16–19]. This led to the idea of using artificial carriers to increase the efficiency of flavonoid penetration to target organs. This method of delivery, on the one hand, increases the penetration and targeted action of higher drug concentrations on specific organs, and on the other hand, reduces its effect on intact cells and tissues.

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Excipients mentioned in the study besides other: Eudragit, chitosan, PLGA, Cyclodextrin

Zverev, Y.F., Rykunova, A.Y. Modern Nanocarriers as a Factor in Increasing the Bioavailability and Pharmacological Activity of Flavonoids. Appl Biochem Microbiol 58, 1002–1020 (2022). https://doi.org/10.1134/S0003683822090149