**2.13. An overview of clay chemistry**

**2.12. 2D clay nanoparticles for drug delivery in cancer treatment**

single-layer composition [106].

**Figure 9.** XRD patterns of MMT and 5-FU-MMT [106].

178 Current Topics in the Utilization of Clay in Industrial and Medical Applications

Two-dimensional kaolinite clay nanoparticles are used in the drug delivery system. The increasing of spacing of the kaolinite nanoparticles from 0.72 to 4.16 nm is due to the interference of guest species with different chain lengths of organic materials that can increase the drug delivery efficiency and reduce the toxicity of doxorubicin (DOX). The kaolinite (Kaolin) and kaolin compounds show a high level of biocompatibility and low toxicity against

**Figure 10.** The schematics of donepezil interference in clay nanomaterials: (a) the dual-layer composition and (b) the

Broadly, clay minerals are structured of two principal units: tetrahedral (T) and octahedral (O) sheets [114, 115]. Each tetrahedron consists of a central cation (mostly Si4+) coordinated to four O<sup>2</sup><sup>−</sup> anions and linked to adjacent tetrahedra through three shared oxygens on the corners (basal oxygens Ob) forming an infinite 2D hexagonal mesh (**Figure 12**). The fourth O<sup>2</sup><sup>−</sup> (apical oxygen Oa) remains unshared, lying perpendicular to the tetrahedral sheet, and is the main site of interaction with the octahedral sheet. Each octahedron consists of a metal cation (*M<sup>n</sup>*<sup>+</sup> ) coordinated to six O2<sup>−</sup> and/or OH− anions. Adjacent octahedra are linked to each other by sharing edges (two O2<sup>−</sup> or OH<sup>−</sup> ), forming an octahedral sheet. If Mn is divalent (Mg2+ ), a trioctahedral or a brucite-like sheet is produced, if it is trivalent (Al3+ ), then two out of every three octahedral sites are occupied, leaving a vacant site and the generation of a dioctahedral or a gibbsite-like sheet. Clays can be classified into 1:1 and 2:1 types according to the layering

**Figure 11.** Schematic design and kaolin and kaolin compounds for the treatment of tumors [113].

of T and O sheets. 1:1 (or T-O) clay minerals consist of a single T sheet linked to a single O sheet, and 2:1 (or T-O-T) clay minerals consist of a single O sheet sandwiched between two T sheets (**Figure 12**, **Table 3**).

In the case of smectites, an octahedral sheet of metal oxides (usually Mg2+ or Al3+ ) is sandwiched between two tetrahedral silica sheets. Two types of charges originate on the smectite clay particle: (1) permanent negative charges on the surface due to isomorphous cation substitution in the tetrahedral and/or octahedral sheets (e.g., Li<sup>+</sup> for Mg2+ in Laponite) balanced by exchangeable cations such as Na or Ca2+ in the interlayer gallery. (2) Positive (amphoteric) charges on the edges due to broken Si-O, Al-OH, and Mg-OH groups. At pH < Zero Point of Charge (ZPC), these edge charges become positive with anion exchange capacity, while at pH > ZPC, they become negative with a cation exchange capacity. Adapted with permission [116]. Copyright 2014, John Wiley and Sons.

*Clay structure and reactivity*. The reactivity of clays is largely a function of their swelling capacity. Kaolinite (of the 1:1 clay family) and talc and pyrophyllite (of the 2:1 clay family) possess no structural charges and consequently are non-swelling and of low adsorption capacity. The high-layer charge on vermiculite and illite restricts their swelling and gelling tendency although their surface area and CEC are relatively high. Smectites are characterized by their relatively low-layer charge which allow their particles to undergo complete dissociation in water and give them interesting rheological/gel-forming properties and surface reactivity. Halloysite is formed of hydrated 1:1 layers which role up into nanotubes (alumina sheet on the inside and silica sheet on the outside surface) and sepiolites (and palygorskite) are characterized by their inverted 2:1 ribbon structures. Such arrangements confer large SSA, porosity, and sorptive capacity. Adapted with permission [117].

kaolin are platy clay particles ranging from nanometers to micrometers, whereas halloysite nanotubes are hollow rod-like particles having a lumen diameter of ∼20 nm and a tube length ranging from 300 nm to 2 μm. Spherical silica nanoparticles were also used as a material mimicking the outer silica layer of the clays. Graphene oxide nanosheets having the shape and size close to smectite clays were selected as a material with a relatively high reported toxicity, 30, which was also confirmed in our study. The typical AFM images demonstrating the geometry

**Table 3.** Key clay mineral species explored for tissue engineering and regenerative medicine applications with their

The nanoparticles used were suspended in water and added to protozoan media at a range of concentrations. Prior to toxicity investigation, the hydrodynamic diameters and surface potential of nanoparticles were determined using dynamic light scattering (DLS) and electro-

No ecotoxicological studies of nanoclay have been identified as of November 30, 2010. Since clay is a naturally occurring material for which environmental organisms have adapted throughout evolution, the inherent toxicity is expected to be low; however, issues related to

Today, few studies are available, and there is limited knowledge about the toxicity of nanoclays and the chemical derivatives that may be generated during the production and processing of polymer nanoclay composites. However, in general, nanoclay is not considered to pose a major health risk although a possible content of crystalline quartz may constitute a risk.

and sizes of nanoparticles used in this study are given in **Figure 13**.

phoretic mobility measurements in water (**Table 4**) [118].

**2.15. Ecotoxicological profile**

**Family group Species Chemical** 

2:1 Smectites Montmorillonite Nam(Al2-mMgm)

Laponite (synthetic hectorite)

relevant structural/compositional properties.

Halloysite Al2

1:1 Serpentinekaolin

> Sepiolitepalygorskite

**formula**

Si2 O5 (OH)<sup>4</sup> .

nH2 O

Si4 O10(OH)<sup>2</sup> .

Si4 O10(OH)<sup>2</sup> .

Sepiolite X\*(Mg, Al, Fe 3þ)<sup>4</sup> (Si,Al)<sup>6</sup> O<sup>15</sup>

nH2 O

(OH)<sup>2</sup> .nH2 O

nH2 O

Nah(Mg3-hLih)

**Charge/formula** 

~0 [114] ~10 meq/100 g

~0.2–0.6 [114] ~80–150 meq/100 g [121, 122]

— ~4–40 meq/100 g

[124, 125]

[121, 122]

Development of Clay Nanoparticles Toward Bio and Medical Applications

**CEC Particle size (nm)**

http://dx.doi.org/10.5772/intechopen.77341

Nanotube diameter of ~50 nm, lumen of ~15 nm, and length of ~1 mm [119, 126]

181

~80–300 nm diameter and ~ 1 nm thickness [127, 129]

~25–30 nm diameter and ~ 1 nm thickness [120, 123]

Nanofiber diameter of ~15 nm and length of ~200–400 nm [124, 128]

**unit**

small particle sizes may occur [78].

**2.16. Toxicological profile**
