Glycyrrhizic Acid as a Novel Drug Delivery Vector: Synergy of Drug Transport and Efficacy

Abstract

Supramolecular drug delivery systems (DDS) are widely used in pharmacology during last decades for designing new preparations with improved properties. Most of fundamental and applied research in this field has been devoted to the inclusion complexes with cyclodextrins (CD), which are assumed to possess protective properties and to decrease the hydrophobic behavior of the included molecules. At present a new generation of DDS has been developing. Novel DDS are focused simultaneously on several purposes, including improved bioavailability and stability of drugs, targeted drug delivery, and enhanced activity. One of the compounds that appear to be promising is glycyrrhizic acid (or glycyrrhizin). A number of experimental facts of high therapeutic activity of glycyrrhizin conjugates have been published, but no understanding "how it works" was presented. This manuscript will highlight our attempts to answer this question using physicochemical approach, and also outline the challenges and future opportunities for medical applications of glycyrrhizin conjugates.

Glycyrrhizic acid as a multifunctional drug carrier – From physicochemical properties to biomedical applications: A modern insight on the ancient drug

“…At the same time, toxicity decreases by 1.7 times, and the amplitude of the therapeutic index increases by 17 times (Tolstikova et al, 2009). Similar action was detected for complexation of glycyrrhizin with other drugs, for example, nifedipine complexes with GA manifested antihypertensive therapeutic effect in a ten-fold reduced dose of nifedipine (Tolstikova et al, 2009;Polyakov and Leshina, 2011). The anti-inflammatory activity of GA and salbutamol was tested using tumor necrosis factor-alpha-induced NF-kappaB transcriptional activation reporter assay, I-kappaB Western blotting and interleukin-8 ELISA.…”

“…Only in last decades in addition to its own therapeutic activity, a novel unusual property of the GA has been discovered. In particular, the ability of GA to form inclusion complexes with a variety of drugs was demonstrated (Baltina, 2003;Apanasenko et al, 2015;Polyakov et al, 2008;Tolstikova et al, 2009;Polyakov and Leshina, 2011;Polyakov et al, 2013). These complexes show significant advantages over other known DDS.…”

<p>One-step mechanochemical preparation and prominent antitumor activity of SN-38 self-micelle solid dispersion</p>

“…Third, it was reported that GA increases drug permeability not only due to increased solubility but also due to increased drug permeability through cell membranes. 20,36 Na 2 GA has similar properties to GA and can penetrate more into the cells than SN-38 suspension, therefore leading to a better bioavailability.…”

“…Disodium glycyrrhizinate (Na 2 GA) is the salt of glycyrrhizic acid (GA) which can undergo hydrolysis in aqueous solutions and form a free GA. Like GAs, it has anti-inflammatory and anti-cancer properties, 20 and the resulting solution is less viscous and can help improve the solubility and permeability of hydrophobic drugs. 21 Considering the environmentfriendly and low-cost mechanochemical techniques and potential dissolution enhancement ability of Na 2 GA, an amorphous solid dispersion of SN-38 was prepared by mechanical milling, which was combined with Na 2 GA. 22 Moreover, we evaluated the physical characteristics, dissolution law, in vitro and in vivo properties, pharmacokinetics, tissue distribution, and antitumor effects.…”

Molecular complexes of the triterpene glycosides with L-tyrosine and their biological activity

“…Introduction. At present more and more attention is paid to the methods of obtaining molecular complexes of different biologically active substances with plant saponins and the elaboration of novel medical preparations on their basis [1][2][3][4][5][6][7][8][9]. In particular, the complexes with aromatic amino acids were synthesized.…”