# Therapeutic Applications of Halloysite
## 3 Halloysite Structure and Applications  
### HNT Structure  
Halloysite nanotubes (HNTs) are naturally occurring aluminosilicate nanoparticles empirical formula Al\({}_{2}\)Si\({}_{2}\)O\({}_{5}\)(OH)\({}_{4}\)) with a chemical composition similar to kaolinite, dickite, or nacrite [37; 38; 39] (Figure 2). However, unlike kaolinite, dickite, and nacrite, the unit layers in halloysite are separated by a monolayer of water molecules [38; 39]. As a result, a hydrated halloysite has a basal (d001) spacing of 10 A, approximately 3 A larger than kaolinite. Halloysite-(10 A) can readily and irreversibly dehydate to give the corresponding halloysite-(7 A) form when halloysite-(10 A) is heated to 90-150 \({}^{\circ}\)C. HNTs can be found in China, France, Belgium, New Zealand, America, and Brazil [40]. The chemical composition for halloysite-(7 A) and halloysite-(10 A) is Al\({}_{2}\)Si\({}_{2}\)O\({}_{5}\)(OH)\({}_{4}\), nH\({}_{2}\)O where n = 0 and 2, respectively [41; 42; 43]. If n is 2, the HNTs are hydrated, and if n is 0, the HNTs are dehydrated [10; 11]. Therefore, AIPEA Nomenclature Committee recommended terms halloysite-(10 A) for the hydrated mineral and halloysite-(7 A) for the dehydrated form.  
The layers of aluminum and silicate with alternating positive and negatively charged layers in halloysite make them suitable adsorbents for cations and anions [41]. Apart from the conventional use of halloysite to manufacture porcelain and in petrochemical applications, halloysite has been explored as a carrier material for drug delivery [37; 38], tissue engineering [41; 42], and wound healing applications [43]. HNTs can adopt a variety of morphologies. For example, an elongated tubule short tubular, spheroidal and platy nanoparticle shapes have been reported [44]. Spheroidal halloysite occurs widely, and it is common to find pseudo-spherical or spheroidal particles in weathered volcanic ashes and pumices [39; 45; 38].  
The hollow tubular form in the submicrometer range is most commonly used. These tubules may be extended and thin, short and stubby, or emerging from other tubes [10]. The halloysite tubules' size varies from 500-1000 nm in length with an outer diameter of 10-50 nm and an inner diameter measuring 5-20 nm depending on the deposit [43; 44; 45]. The neighboring alumina and silica layers, their hydration layers, create a packing disorder that induces curvature and the layers roll up, forming multilayer tubes. The HNT external surface comprises O-Si-O bonds with terminal hydroxyl groups [37; 38]. The inner lumen comprises O-Al-O bonds, terminating in hydroxyl groups [46; 47]. At pH 8.5 and below, these inner hydroxyl groups are mostly protonated, resulting in a positively charged inner lumen.  
A wide range of active agents, including antibiotics, cancer drugs, marine biocides, and biological molecules, can be entrapped within the inner lumen and void spaces within the aluminosilicate shells [48; 49; 50; 47]. HNTs nanotubes are non-cytotoxic on several cell types (up to concentrations of 0.1 mg/mL), including chondrocytes, dermal fibroblasts, osteoblasts, and stem cells on halloysite nanofilms or within HNT-hydrogel composites [48; 49; 50; 51; 52; 53; 54]. Examination of halloysite with in-vitro assays showed cells proliferated and maintained their cellular phenotype. Recent biocompatibility studies have shown that HNTs do not provoke a cytotoxic or host immune response [51; 52]. As halloysite nanotubes have been shown to exhibit high biocompatibility levels and very low cytotoxicity, it represents an ideal candidate for new drug delivery and polymer systems.  
Figure 2: The structure of halloysite and its potential for surface modification.