1. Introduction
Researchers have defined hydrogels in many different ways, but nowadays the most accepted definition is the existence of a three-dimensional network, formed by the cross-linking of polymeric chains, that possesses the capability to swell thanks to the presence of hydrophilic groups and to maintain a very high amount of water in its structure [
1,
2]. Since their discovery, hydrogels have received attention from the scientific community due to the wide range of applications they can be used for: Environmental issues like water remediation, drug delivery systems and tissue engineering, cosmetic and food packaging industry, and oil spill recovery [
3,
4,
5,
6,
7,
8]. Furthermore, with the evolution of nanotechnology, the challenge to design and prepare hydrogels with specific and requested features at the nano-scale led to the development of nanohydrogels. Among the different polymeric species that can be used to achieve this aim, polysaccharides cover a marked importance, especially in the preparation of the so-called “polysaccharide-based natural hydrogels”, for some of their most peculiar properties such as water solubility and swelling capacity, biocompatibility and biodegradability, self-healing and pH sensitivity that are crucial for their use [
9,
10]. Moreover, the possibility to modify the structure of the polysaccharides and the adaptability of their networks allows for the development of eco-friendly smart materials [
11,
12]. To date, the most widely used raw materials include natural biopolymers such as chitosan, alginate, pectin and cellulose. One of the major factors limiting the use of nanohydrogels is their structural instability, thus making necessary the use, among others, of inorganic nanoparticles to overcome them [
13,
14,
15,
16].
Among clays, halloysite nanotubes (HNTs) have great importance thanks to their own main characteristics [
17]. HNTs are a naturally occurring alumino-silicate whose structural formula is Al
2Si
2O
5(OH)
4·nH
2O, where Al is disposed in an gibbsite-like octahedral organization of Al–OH groups whereas Si–O groups form a tetrahedral sheet [
18,
19]. Both aluminols and siloxanes layers are overlapped in a kaolinite typical sheet that rolls up due to some structural defects and to the presence of water molecules, thus giving halloysite its peculiar narrow nanotubular structure [
20,
21,
22].
HNTs dimensions depend on the natural deposit the clay is extracted from. In particular, the internal and external diameters are approximately 10–15 and 50–80 nm respectively, while the nanotubes length can range from 100 nm to 2 µm. [
19] Interestingly, it is possible to classify halloysite by considering the distance between interlayers. For instance, it can be 7 or 10 Å depending on the number of water molecules present between the layers, which is namely 0 or 2, respectively [
23,
24]. Moreover, one of halloysite’s most fascinating and important features is the different charge, in the pH interval from 3 to 8, between the outer surface that is mainly composed of Si–O groups and negatively charged, and the inner surface that is mainly composed of Al–OH and positively charged [
25,
26]. This different charge, due to the chemical composition, allows for selective functionalization, exploiting both the covalent and electrostatic interactions of each surface with other oppositely charged species: Drug molecules, polysaccharides, proteins, lipids, surfactants and so on [
27,
28,
29]. All these features, and also considering that they are low cost, eco- and biocompatible materials [
30], make HNTs suitable for designing hybrid materials for waste water remediation [
31,
32,
33,
34,
35], cultural heritage treatment [
36,
37], biotechnological applications [
38,
39,
40,
41,
42,
43,
44], and packaging [
45,
46,
47,
48,
49,
50].
Notably, halloysite is commonly used as a component in drug delivery systems through exploiting its characteristics in combination with other organic moieties, for example the temperature responsive polymers such as poly(N-isopropylacrylamide) (PNIPAAMs) that can selectively interact with the inner/outer surfaces thus influencing the release kinetics by changing their adsorption site [
51], or natural occurring biopolymers for the preparation of end capped nanotubes with smart gates, or reverse inorganic micelles for the formation of nanohydrogels inside the HNTs lumen for a triggered absorption or release [
52,
53].
As evidenced in a recent review [
17], the combination of polymer hydrogels and hollow inorganic nanotubes represents a perspective strategy for the fabrication of functional carriers in an advanced application.
In this work, we prepared hydrogel beads based on chitosan containing halloysite nanotubes. An alginate layer was introduced by diffusion and immersion of the beads in a sodium alginate solution. The dispersion of nanotubes into the hybrid gel and the localization of the alginate was investigated by SEM and fluorescence microscopy. Doxycycline, an antibiotic of the tetracycline class, was used as the model drug and it was loaded into the halloysite cavity by using a literature protocol [
54]. This work represents a promising step for a valid alternative to generate hybrid hydrogels with oppositely charged polysaccharides and nanoclay with specific morphology for controlled drug release.