## 1 Introduction  
Flavones are a class of naturally occurring compounds, resultants of plant metabolic processes [1; 2], and found in a variety of plant products. Flavones fulfill different roles in protecting plants against various external factors such as microorganisms, herbivores, or UV radiation [3].  
Flavones have sparked interest in broad medical research due to their antioxidant [4], antibacterial [5], antiviral [6], anti-inflammatory [7; 8], anticancer [9; 10], anti-ischemic [11], hypolipidemic [12], antimutagenic [13], and immune-stimulating properties [14].  
From a chemical point of view, the basic structure is a benzopyran nucleus to which a benzene ring is grafted. The backbone structure is commonly described in the literature as C6-C3-C6 (Figure 1) [15; 16; 17].  
5-Hydrooxyflavone, or primuletin (5-hydroxy-2-phenyl-4_H_-1-benzopyran-4-one) (Figure 2), is a naturally occurring flavone identified in _Primula_[18] and _Dionysia_ species [19] and has a single hydroxyl group at the 5 position on the flavone core. Thus, 5-hydroxyflavone has two adjacent centers that can donate electrons to chelate metal ions and, along with the planarity of the molecule, primuletin can act as a bidentate ligand in complexation reactions with metal ions [20; 21].  
Metal complexes of 5-hydroxyflavone with magnesium [22], zinc [22], copper [23], iron [23], chromium [24; 25], samarium [21], europium [21], gadolinium [21], terbium [21], aluminum [26], gallium [26], and indium [26] have been described in the literature, revealing that through complexation processes, the pharmacological properties of ligands can be modified, with the effects of complexes being in most cases more pronounced than those of ligands alone [21; 23; 27; 28; 29; 30; 31].  
As the limited solubility of complexes in aqueous media was considered a potential disadvantage [32; 33], new techniques have been developed over time to overcome this impediment [34]. In particular, cyclodextrin-derived nanosponges as transport systems have been obtained through the polycondensation of cyclodextrin molecules with crosslinking agents. By joining cyclodextrin molecules, a three-dimensional network is formed. In the network cavities, substances are incorporated, thereby increasing the solubility [35; 36; 37].  
For example, camptthecin is a substance with limited solubility in water and chemical instability due to the lactone ring [38]. To overcome these drawbacks, the active substance has been incorporated into nanosponges. The superior antitumor activity of the formed inclusion complex was demonstrated by in vivo and in vitro studies [39]. Cyclodextrin-derived nanosponges represent a biocompatible and nontoxic carrier agent solution for preclinical studies, improving the pharmacokinetic and pharmacodynamic profiles of the transported substances [40]. CRLX101 represents a novel nanosubstance synthesized using a novel method called \"self-assembly\". Camptthecin is covalently linked to the cyclodextrin polymer using a crosslinker. This derivative polymer can additionally encapsulate  
Figure 1: The general chemical structure of flavonoids.  
Figure 2: Structure of 5-hydroxyflavone.  
campotthecin molecules, and the potential of this nanomedicine has been studied in clinical trials on a diverse range of cancers such as lung, renal, and ovarian [41].  
The purpose of the present study is to characterize the interactions between aluminum and gallium complexes with 5-hydroxyflavone and the three-dimensional structure of cyclodextrin nanosponges and evaluate the pharmacological properties of the complexes.