Marina Massaro

Development and characterization of co-loaded curcumin/triazole-halloysite systems and evaluation of their potential anticancer activity.

Positively charged halloysite nanotubes functionalized with triazolium salts (f-HNT) were employed as a carrier for curcumin molecules delivery. The synthesis of these f-HNT new materials is described. Their interaction with curcumin was evaluated by means dynamic light scattering (DLS) and UV-vis spectroscopy in comparison with pristine unmodified HNT (p-HNT). The curcumin load into HNT was estimated by thermogravimetric analysis (TGA) measurements, while the morphology was investigated by scanning electron microscopy (SEM) techniques. Release of curcumin from f-HNT, at three different pH values, by means of UV-vis spectroscopy was also studied. Furthermore, different cancer cell lines were used to evaluate the potential cytotoxic effect of HNT at different concentrations and culture times. The results indicated that the f-HNT drug carrier system improves the solubility of curcumin in water, and that the drug-loaded f-HNT exerted cytotoxic effects against different cell lines.

Direct chemical grafted curcumin on halloysite nanotubes as dual-responsive prodrug for pharmacological applications.

Covalently functionalized halloysite nanotubes (HNTs) were successfully employed as dual-responsive nanocarriers for curcumin (Cur). Particularly, we synthesized HNT-Cur prodrug with a controlled curcumin release on dependence of both intracellular glutathione (GSH) and pH conditions. In order to obtain HNT-Cur produgs, halloysite was firstly functionalized with cysteamine through disulphide linkage. Afterwards, curcumin molecules were chemically conjugated to the amino end groups of halloysite via Schiffs base formation. The successful functionalization of halloysite was proved by thermogravimetric analysis, FT-IR spectroscopy, dynamic light scattering and scanning electron microscopy. Experimental data confirmed the presence of curcumin on HNT external surface. Moreover, we investigated the kinetics of curcumin release by UV-vis spectroscopy, which highlighted that HNT-Cur prodrug possesses dual stimuli-responsive ability upon exposure to GSH-rich or acidic environment. In vitro antiproliferative and antioxidant properties of HNT-Cur prodrug were studied with the aim to explore their potential applications in pharmaceutics. This work puts forward an efficient strategy to prepare halloysite based nanocarriers with controlled drug delivery capacity through direct chemical grafting with stimuli-responsive linkage.

Halloysite nanotubes loaded with peppermint essential oil as filler for functional biopolymer film

The purpose of this paper is to show how a functional bionanocomposite film with both antioxidant and antimicrobial activities was successfully prepared by the filling of a pectin matrix with modified Halloysite nanotubes (HNT) containing the essential peppermint oil (PO). Firstly, HNT surfaces were functionalized with cucurbit[6]uril (CB[6]) molecules with the aim to enhance the affinity of the nanofiller towards PO, which was estimated by means of HPLC experiments. The HNT/CB[6] hybrid was characterized by several methods (thermogravimetry, FT-IR spectroscopy and scanning electron microscopy) highlighting the influence of the supramolecular interactions on the composition, thermal behavior and morphology of the filler. Then, a pectin+HNT/CB[6] biofilm was prepared by the use of the casting method under specific experimental conditions in order to favor the entrapment of the volatile PO into the nanocomposite structure. Water contact angle measurements, thermogravimetry and tensile tests evidenced the effects of the modified filler on the thermo-mechanical and wettability properties of pectin, which were correlated to the microscopic structure of the biocomposite film. In addition, PO release in food simulant solvent was investigated at different temperatures (4 and 25°C), whereas the antioxidant activity of the nanocomposite film was estimated using the DPPH method. Finally, we studied the in vitro antibacterial activity of the biofilm against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive), which were isolated by beef and cow milk, respectively. These experiments were carried out at specific temperatures (4, 37 and 65°C) that can be useful for a multi-step food conservation. This paper puts forwards an easy strategy to prepare a functional sustainable edible film with thermo-sensitive antioxidant/antimicrobial activity.

Functionalized halloysite multivalent glycocluster as a new drug delivery system

A new design for halloysite nanotube materials was obtained by grafting chemically modified cyclodextrin units onto the nanotube surface. In particular, grafted cyclodextrins were decorated with thiosaccharide pendants, in order to mimic the well-known binding of sugars to proteins and the glyco-cluster effect occurring during cellular recognition events. The obtained materials were characterized by using a combination of varied techniques (FT-IR spectroscopy, thermogravimetric analysis, scanning electron microscopy, dynamic light scattering, turbidimetry), and their potential drug-delivery abilities were tested by studying their interactions with the common naturally occurring anticancer agent curcumin. A suitable model describing the interaction between our materials and curcumin is proposed.

Covalently modified halloysite clay nanotubes: synthesis, properties, biological and medical applications

Halloysite (HNT) is a promising natural nanosized tubular clay mineral that has many important uses in different industrial fields. It is naturally occurring, biocompatible, and available in thousands of tons at low cost. As a consequence of a hollow cavity, HNT is mainly used as nanocontainer for the controlled release of several chemicals. Chemical modification of both surfaces (inner lumen and outer surface) is a strategy to tune the nanotubes properties. Specifically, chemical modification of HNT surfaces generates a nanoarchitecture with targeted affinity through outer surface functionalization and drug transport ability from functionalization of the nanotube lumen. The primary focus of this review is the research of modified halloysite nanotubes and their applications in biological and medical fields.

Multicavity halloysite–amphiphilic cyclodextrin hybrids for co-delivery of natural drugs into thyroid cancer cells

Multicavity halloysite nanotube materials were employed as simultaneous carriers for two different natural drugs, silibinin and quercetin, at 6.1% and 2.2% drug loadings, respectively. The materials were obtained by grafting functionalized amphiphilic cyclodextrin onto the HNT external surface. The new materials were characterized by FT-IR spectroscopy, SEM, thermogravimetry, turbidimetry, dynamic light scattering and ζ-potential techniques. The interaction of the two molecules with the carrier was studied by HPLC measurements and fluorescence spectroscopy, respectively. The release of the drugs from HNT-amphiphilic cyclodextrin, at two different pH values, was also investigated by means of UV-vis spectroscopy. Biological assays showed that the new complex exhibits anti-proliferative activity against human anaplastic thyroid cancer cell lines 8505C. Furthermore, fluorescence microscopy was used to evaluate whether the carrier was uptaken into 8505C thyroid cancer cell lines. The successful results revealed that the synthesized multicavity system is a material of suitable size to transport drugs into living cells.

Pharmaceutical properties of supramolecular assembly of co-loaded cardanol/triazole-halloysite systems.

Halloysite nanotubes were explored as drug carrier for cardanol, which is considered as a promising natural anticancer active species. To this aim, besides the pristine nanoclay, a chemical modification of the nanocarrier was performed by attaching triazolium salts with different hydrophobicity at the outer surface of the hollow nanotubes. The interaction between cardanol and nanotubes was highlighted in solution by HPLC. This method proved the loading of the drug into the nanotubes. The solid dried complexes formed by pristine and modified halloysite with the cardanol were characterized by IR spectroscopy, thermogravimetric analysis as well as water contact angle to evidence the structure, thermal properties and wettability of the obtained materials. The kinetics of cardanol release as well as cell viability experiments provided promising results that put forward a new strategy for potential applications of cardanol as active antiproliferative molecule and clay nanotubes as drug carrier.

Halloysite nanotubes as support for metal-based catalysts

Halloysite nanotubes (HNTs) are clay minerals with a hollow nanotubular structure. There is growing interest in these nanomaterials, due to their biocompatibility, potential applications and availability. The surface chemistry of HNTs is versatile for the targeted chemical modification of the inner lumen and outer surface. Functionalized halloysite constitutes a valuable support for metal nanoparticles, promoting catalytic applications with tunable properties. The peculiar tubular shape of HNTs favors the dispersion and surface availability of the supported metal nanoparticles that are active in the catalytic path. Moreover, the presence of an empty lumen opens new perspectives for the production of nanoarchitectures with synergistic catalytic effects, due to the increase in local concentrations and confinement. The main focus of this review is the research on modified halloysite nanotubes for the preparation of valuable supports for metal nanoparticles and their applications in catalytic processes.

Design of PNIPAAM covalently grafted on halloysite nanotubes as a support for metal-based catalysts

A thermo-responsive polymer such as poly(N-isopropylacrylamide) (PNIPAAM) was covalently grafted on the external surface of halloysite nanotubes (HNTs) by means of microwave irradiation. This nanomaterial was used as a support and stabilizer for palladium nanoparticles. The obtained HNT–PNIPAAM/PdNPs was characterized by means of TGA, SEM, EDS and TEM analyses. The palladium content of the catalyst was estimated to be 0.4 wt%. The stability of the catalytic material at different temperatures (below and above the PNIPAAM lower critical solution temperature) was tested in the Suzuki reaction under microwave irradiation. In addition, TEM analysis after five consecutive runs was performed. The catalyst showed a good catalytic activity toward the Suzuki cross-coupling reaction between phenylboronic acid and several aryl halides in aqueous media under microwave irradiation and low palladium loading (0.016 mol%, 8 μg of Pd). Turnover numbers (TONs) and frequencies (TOFs) up to 6250 and 37 500 h−1, respectively, were reached. The catalyst was easily separated from the reaction mixture by centrifugation and reused for five consecutive cycles with a small drop in its catalytic activity.

Dual drug-loaded halloysite hybrid-based glycocluster for sustained release of hydrophobic molecules

A dual drug-loaded HNT–CD glycocluster delivery system based on halloysite nanotubes and carbohydrate functionalized cyclodextrin was developed by a green protocol using solvent-free microwave irradiation. The nanohybrid was employed for concurrent load and release of silibinin and curcumin. The new delivery system was characterized by means of TGA, FT-IR spectroscopy, SEM and DLS. These techniques confirm the successful loading of the two drugs in the system. SEM and DLS measurements highlighted that the nanomaterial preserves a tubular structure with an average hydrodynamic radius of ca. 200 nm. The release of the drugs from the HNT glycocluster was investigated by means of UV-vis spectroscopy at two different pH values simulanting the typical physiological conditions of either gastric or intestinal fluids. Enzyme-linked lectin assays (ELLA) demonstrated that highly mannoside–cyclodextrins HNT entities display high affinity towards mannose selective ConA lectin. Biological assays showed that the new drug delivery system exhibits anti-proliferative activity against the investigated cell lines. Fluorescence microscopy confirmed ELLA results and it showed a high propensity of this drug delivery system to cross cell membranes and to penetrate into the cell nucleus. The results revealed that the synthesized multicavity system is a material of suitable size and nanoarchitecture to transport drugs into living cells.