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 nanotube's 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.

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

Correction for 'Covalently modified halloysite clay nanotubes: synthesis, properties, biological and medical applications' by M. Massaro et al., J. Mater. Chem. B, 2017, 5, 2867-2882.

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.

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 Schiff's 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.

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.

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.

Temperature-controlled poly(propylene) glycol hydrophobicity on the formation of inclusion complexes with modified cyclodextrins. A DSC and ITC study.

The study highlighted the main forces driving the formation of hydroxypropyl-cyclodextrins (HP-CDs) + poly(propylene) glycol 725 g mol(-1) inclusion complexes. The temperature parameter was chosen as the variable to modulate the hydrophobicity of the polymer, and consequently ITC experiments as functions of temperature as well as DSC measurements were done in a systematic way. The polymer is not included into HP-α-CD, it is strongly bound to HP-ß-CD and it is floating in HP-γ-CD. The stability of the inclusion complexes is entropy controlled. The gain of the entropy is a unique result compared to the opposite literature findings for inclusion complexes based on polymers and CDs. This peculiarity is ascribable to the removal of water molecules from cages during complexation and this effect compensates the entropy loss due to constraints caused by the CD threading. In spite the host-guest van der Waals contacts are optimized, the enthalpies for the inclusion complex formation are positive and reveal the large heat required for dehydrating the propylene oxide units. All the macrocycles enhanced the polymer solubility in water. Increasing the affinity of the macrocycle to the macromolecule makes more expanded the one-phase area of the binodal curve. A new thermodynamic approach was proposed to predict quantitatively the binodal curve as well as the dependence of the enthalpy of separation phase on the macrocycle composition. The agreement between the experimental data and the computed values was excellent.

Extended investigation of the aqueous self-assembling behavior of a newly designed fluorinated surfactant.

The physicochemical behavior of the newly synthesized fluorinated 5-hydroxyamino-3-perfluoroheptyl-1,2,4-oxadiazin-6-one (PFHO) surfactant was investigated. Thermal analysis showed that the pure surfactant is thermally stable under an inert atmosphere to 135 degrees C, which is several degrees higher than the melting point (99 degrees C). PFHO is rather active at the water/air interface where it assumes a standing up configuration. It exhibits an enhanced self-assembling behavior; accordingly, the critical micellar concentrations at some temperatures are 2 orders of magnitude lower than those of a similar surfactant having the same phobicity, such as sodium perfluorooctanoate. Even in the dilute domains, PFHO forms large micelles, detected by dynamic light scattering studies, that are precursors of the gel occurring at rather low composition (only 2.0% w/w at 25 degrees C). Optical microscopy evidenced cylindrical aggregates in gel systems whereas differential scanning calorimetry and viscosity showed that the gels are stable over a wide temperature range to ca. 70 degrees C where they undergo a reversible gel --> fluid transition. Finally, percolation theory combined with data provided by the experimental studies enabled us to predict the PFHO gelation process correctly, in very good agreement with the experimental findings.

Copolymer-cyclodextrin inclusion complexes in water and in the solid state. A physico-chemical study.

The formation of inclusion complexes (ICs) composed of cyclodextrins (CDs) and poly(ethylene oxides)-poly(propylene oxides)-poly(ethylene oxides) (PEO-PPO-PEO) was studied. To this purpose, native and hydroxypropyl cyclodextrins with different cavity size were chosen. The PEO-PPO-PEO copolymers were selected to study the role of the molecular weight, keeping constant the hydrophilic/hydrophobic ratio, and the hydrophilicity. The volumetric studies at 25 degrees C allowed to determine the equilibrium constant and the volume change for the IC formation in water as well as the IC stoichiometry. Surface tension experiments evidenced that the copolymer and the CD interfacial behavior is controlled by the formation of ICs taking place in the bulk phase. It was proved that the differential scanning calorimetry (DSC) is a valid method to describe quantitatively the IC in the solid state. The combination of volumes, DSC and FTIR techniques together with the geometric information highlighted the following points: (1) the included copolymer is in the amorphous state; (2) the IC composed of native CDs adopts a channel structure with two EO units incorporated into one CD molecule; (3) the IC composed of hydroxypropyl-cyclodextrin is a polymeric structure like a necklace decorated with CD rings. Finally, TGA experiments showed that the thermal stability of the IC depends on the nature of both components.

Aqueous laponite clay dispersions in the presence of poly(ethylene oxide) or poly(propylene oxide) oligomers and their triblock copolymers.

The effect of polyethylene oxide (PEO) or polypropylene oxide (PPO) oligomers of various molecular weight (Mw) as well as of triblock copolymers, based on PEO and PPO blocks, on aqueous laponite RD suspensions was studied with small-angle neutron scattering (SANS). The radius of gyration (RG) increases for low M w whereas the opposite occurs for larger Mw. This behavior is explained on the basis that an effective R G is given by two contributions: (1) the size of the particles coated with the polymer and (2) the interactions between the laponite RD particles which are attractive for small and repulsive for large polymers. The SANS curves in the whole Q-range are well described by a model of noninteracting polydisperse core+shell disks, where the thickness of the polymer layer increases with the Mw. The adsorbed polymer is in a more compact conformation compared to a random coil distribution while the fraction of the polymer in the shell formed around the laponite RD particles is nearly independent of Mw. For increasing laponite RD amounts, at a given polymer composition, the thickness of the polymer slightly changes. In some cases, where also gelation is sped up, a structure factor with attractive interaction was employed which allowed to evaluate the attractive forces between the laponite RD particles. The gelation time was determined for mixtures at fixed copolymer and laponite RD concentrations. Surprisingly, it is observed that gels are formed despite the fact that the binding sites of the laponite RD particles are almost covered but the polymer size is too small to prevent aggregation. The gelation rate is correlated to structure and thermodynamics of these systems. Namely, when the balance between the steric forces and the depletion attractive forces undergoes an abrupt change the gelation time also undergoes a sharp variation. For lower and comparable Mw, PPO speeds up the gelation more efficiently than PEO while for higher Mw the gelation kinetics is slowed down again. Interestingly, copolymers of PEO and PPO blocks do not induce gelation in the time-window where the homopolymers do.

Solubilization of an organic solute in aqueous solutions of unimeric block copolymers and their mixtures with monomeric surfactant: volume, surface tension, differential scanning calorimetry, viscosity, and fluorescence spectroscopy studies.

The ability of aqueous systems, formed by unimeric copolymers and their mixtures with a monomeric surfactant, in solubilizing large quantities of 1-nitropropane (PrNO2) was explored. The copolymers are F68 and L64, which differ for the hydrophilicity, and the surfactant is sodium dodecanoate. For a better understanding of the mechanism of solubilization, thermodynamic (volume and differential scanning calorimetry), spectroscopy (steady-state fluorescence), viscosity, and interfacial investigations were carried out. PrNO2 causes the micellization of the unimeric copolymer, and the required amount of PrNO2 depends on the composition, the copolymer nature, and the temperature. Large quantities of PrNO2 form mixed micelles where PrNO2 experiences an environment similar to its pure liquid state. The presence of the additive allows a decrease of the critical micellar temperature, evidence of which is quantitatively explained through a novel thermodynamic approach. A synergistic effect in solubilizing PrNO2 was observed when surfactant monomers were added to the unimeric copolymer solutions. The increased amount of PrNO2 leads to the complete self-assembling of both the copolymer and the surfactant; a process favored by temperature increase. For all of the investigated systems, the presence of PrNO2 generates a viscosity increase.

Polystyrene nanoparticles in the presence of (ethylene oxide)13(propylene oxide)30(ethylene oxide)13, N,N-dimethyloctylamine-N-oxide and their mixtures. A calorimetric and dynamic light scattering study.

Polystyrene nanoparticles were synthesized by emulsion polymerization of styrene. They were functionalized using the conventional surfactant N,N-dimethyloctylamine-N-oxide (ODAO), the tri-block copolymer (ethylene oxide)(13)(propylene oxide)(30)(ethylene oxide)(13) (L64) and their mixtures. To this purpose, dynamic light scattering and calorimetric experiments were carried out and provided information consistent to each other. The L64 adsorption is Langmuir-type in the copolymer dilute regime and generates complex structures at larger concentrations. In the region where ODAO is in the unimeric state, the adsorption process is cooperative leading to hemi-micelle formation at the polystyrene nanoparticle/water interface. In the concentrated region (above the critical micellar concentration), ODAO forms micelles which interact with the solid substrate most likely through ion-dipole forces. The ODAO addition to the dispersion containing polystyrene particles already wrapped by L64 creates an ODAO thickness around the dispersed particles the size of which is equal to that in the absence of the copolymer, but is built at much lower concentrations. A plausible interpretation of this behavior is that the adsorbed L64 confers to the nanoparticles surface novel properties which enhance the attractive forces with the ODAO molecules.

Aqueous block copolymer-surfactant mixtures and their ability in solubilizing chlorinated organic compounds. A thermodynamic and SANS study.

Within the topic of surfactant enhanced solubilization of additives sparingly soluble in water, volumetric, solubility, conductivity, and small-angle neutron scattering (SANS) experiments on mixtures composed of alpha,omega-dichloroalkane, surfactant, copolymer, and water were carried out at 298 K. The triblock copolymers (ethylene oxide)132(propylene oxide)50(ethylene oxide)132 (F108) and (ethylene oxide)76(propylene oxide)29(ethylene oxide)76 (F68) were chosen to investigate the role of the molecular weight keeping constant the hydrophilic/hydrophobic ratio. The selected surfactants are sodium decanoate (NaDec) and decyltrimethylammonium bromide (DeTAB) with comparable hydrophobicity and different charged heads. The alpha,omega-dichloroalkanes were chosen as contaminant prototypes. For the water + surfactant + copolymer mixtures, both the volume and the SANS results straightforwardly evidenced that (1) monomers of NaDec and copolymer unimers generate small mixed aggregates, (2) monomers of DeTAB combined with copolymer unimers do not form aggregates, and (3) unimeric copolymer is solubilized into NaDec and DeTAB micelles. The alpha,omeaga-dichloroalkanes presence induces the F108 aggregation even at very low copolymer composition. The addition of surfactant disintegrates the F108 aggregates and, consequently, the additive is expelled into the aqueous phase. Once F108 is in the unimeric state, it forms copolymer-micelle aggregates which incorporate the oil. In the case of F68 both the volumetric and the SANS data reveal that the additive does not alter the copolymer unimeric state. Moreover, they show that for the aqueous DeTAB-F68 system the additive trapping in both the copolymer-micelle aggregate and the pure micelles takes place being enhanced in the former aggregate in agreement with solubility experiments. For the NaDec-F68 mixtures, an additional solubilization process in the premicellar copolymer-surfactant microstructures occurs. SANS and conductivity data show that the additive incorporation into the mixed and the pure micelles does not essentially influence the structural properties of the aggregates.

Aqueous nonionic copolymer-functionalized laponite clay. A thermodynamic and spectrophotometric study to characterize its behavior toward an organic material.

The affinity of functionalized Laponite clay toward an organic material in the aqueous phase was explored. Functionalization was performed by using triblock copolymers based on ethylene oxide (EO) and propylene oxide (PO) units that are EO(11)PO(16)EO(11) (L35) and PO(8)EO(23)PO(8) (10R5). Phenol (PhOH) was chosen as organic compound, which represents a contaminant prototype. To this purpose, densities and enthalpies of mixing as well as PhOH UV-absorption spectra were determined. The enthalpy and the spectrophotometry revealed PhOH-Laponite interactions whereas the volume did not. It emerged that the area occupied by PhOH on the Laponite surface is equal to that computed from the partial molar volume of PhOH in water, corroborating the insensitivity of the experimental volumes to the adsorption process. The situation where both PhOH and copolymer are simultaneously present in the aqueous Laponite suspension was also investigated. It turned out that the copolymer replaces PhOH from the water/Laponite clay interface, resulting in L35 being the more efficient. Moreover, the lateral copolymer-phenol interactions enhance the anchoring of PhOH to the solid surface. The reverse copolymer exercises the most important relevant effect. The UV-absorption spectra of PhOH in the water + copolymer + Laponite mixtures provided information that is consistent with those given by the calorimetric experiments. In conclusion, the aqueous copolymer-functionalized Laponite presents surface properties very different from the bare Laponite, favoring the removal of the organic compound from the solid surface.

The solubilisation behaviour of some dichloroalkanes in aqueous solutions of PEO-PPO-PEO triblock copolymers: a dynamic light scattering, fluorescence spectroscopy, and SANS study.

The aggregation behaviour of PEO-PPO-PEO triblock copolymers in water and in water + chlorinated additive mixtures was studied by means of fluorescence spectroscopy, dynamic light scattering (DLS), and small-angle neutron scattering (SANS). The copolymers were chosen such as to investigate the effects of molecular architecture (L35 and 10R5) and molecular weight by keeping constant the hydrophilic/hydrophobic balance (F88 and F108). 1,2-Dichloroethane was used as a prototype of water basins contaminants. The hydrodynamic radius of the block copolymer aggregates (R(h,M)) and the intensity ratio of pyrene of the first and the third vibrational band (I(1)/I(3)) were determined as a function of temperature (10-45 degrees C) and concentration. The copolymer architecture essentially does not affect R(h,M) in the entire range of temperature and concentration investigated. At a given temperature, increasing macromolecular size leads to a decrease of R(h,M). With rising temperature R(h,M) also decreases. According to the DLS results, the I(1)/I(3) change with temperature clearly detects the aggregation only for F88 and F108. The presence of 1,2-dichloroethane, at concentrations close to its solubility in water, does not lead to changes in the distribution of hydrodynamic radii for L35 and 10R5. Larger quantities of additive induce the formation of quite polydisperse mixed aggregates for L35 and of networks for 10R5. In the case of F88 and F108, low concentrations of additive lead to formation of mixed aggregates with smaller R(h,M). The SANS results corroborate the DLS and fluorescence findings proving enhancement of the copolymer aggregation through the presence of 1,2-dichloroethane. The DLS findings combined with those from the fluorescence spectroscopy provide some insight into the site of solubilisation of the additive in the aggregates.

A thermodynamic study to evidence the alpha,omega-dichloroalkane/ block copolymer mixed aggregates formation: effect of the copolymer architecture.

The thermodynamics of alpha,omega-dichloroalkanes in aqueous solutions of (ethylene oxide)(11)(propylene oxide)(16)(ethylene oxide)(11) (L35) and (propylene oxide)(8)(ethylene oxide)(23)(propylene oxide)(8) (10R5) was determined at 298 and 305 K. Modeling the experimental data allowed to calculate the standard free energy (DeltaG(D)(o)/w) and the volume (DeltaV(D)/w) for the additive-copolymer mixed aggregates formation per additive molecule. DeltaG(D)(o)/w for Cl(2)CH(2) and Cl(2)(CH(2))(2) evidenced that the process is controlled by the forces exercising between the chlorine atoms and the OH groups of the copolymer micelles protruded into the aqueous phase. Cl(2)(CH(2))(3) experiences both the hydrophilic and hydrophobic domains into the aggregates. The hydrophobic interactions are more significant in 10R5 whereas the hydrophilic ones are more significant in L35. Temperature increase does not influence DeltaG(D)(o)/w in 10R5, whereas, it does influence DeltaG(D)(o)/w in L35, enhancing the ability of the aggregate to extract the chlorinated compounds from the aqueous phase. The DeltaV(D)/w values are consistent with the free energy results. These insights agree with those predicted by the Flory liquid lattice theory. The calculations extended to several alpha,omega-dichloroalkanes showed that Cl(2)CH(2) and Cl(2)(CH(2))(2) prefer poly(ethylene oxide) (PEO), Cl(2)(CH(2))(3) exhibits the same affinity for both PEO and poly(propylene oxide) (PPO), whereas the more hydrophobic additives show a preference for PPO. The copolymer architecture plays a relevant role in the alpha,omega-dichloroalkane solubilization into the polymeric aggregates.

Adsorption of triblock copolymers and their homopolymers at laponite clay/solution interface. Role played by the copolymer nature.

The adsorption thermodynamics of copolymers, based on ethylene oxide (EO) and propylene oxide (PO) units, at the laponite (RD) clay/liquid interface was determined at 298 K. The copolymer nature was tuned at molecular level by changing the hydrophilicity, the architecture and the molecular weight (Mw) keeping constant the EO/PO ratio. Polyethylene (PEGs) and polypropylene (PPGs) glycols with varying Mw and their mixture were also investigated to discriminate the role of the EO and the PO segments in the adsorption process. Enthalpies of transfer of RD, at fixed concentration, from water to the aqueous macromolecule solutions as functions of the macromolecule molality were determined. They were treated quantitatively by means of a model based on two equilibria: (1) one-to-one binding between the macromolecule and the site on the solid and (2) two-to-one binding following which one macromolecule interacts with another one adsorbed onto the solid. The good agreement between the equilibrium constants obtained from calorimetry and those determined from kinetic experiments confirmed the reliability of the experimental and theoretical approaches. Almost all of the systems investigated are highlighted by the one-to-one binding; the L35 and 10R5 systems present both equilibria. The insights provided by the thermodynamics of adsorption of their homopolymers onto RD were fruitful in obtaining detailed information on the nature of the forces involved between RD and the copolymers. The data obtained in the present work clearly evidenced that for comparable polymer Mw, PPG is more suitable in building up a steric barrier around the RD particles and, indeed, exhibits several advantages and no drawbacks. Moreover, the parent copolymers may properly functionalize the RD surface by exploiting both their high affinity to the solid surface and the ability to self-assemble onto it as L35 and 10R5 clearly showed.

Heat capacity of transfer of (Ethylene oxide)13-(propylene oxide)30-(ethylene oxide)13 from water to the aqueous anionic surfactant solutions at 298 K. A quantitative treatment.

Heat capacities of transfer (DeltaCpt) of unimeric (ethylene oxide)13-(propylene oxide)30-(ethylene oxide)13 from water to the aqueous surfactant solutions as functions of the surfactant concentrations (mS) were determined at 298 K. The surfactants investigated are sodium hexanoate, sodium heptanoate, sodium octanoate, sodium undecanoate, and sodium dodecanoate. For short alkyl chain surfactants, the profiles of the DeltaCpt versus mS curves show maxima and minima; for long alkyl chain surfactants, the maximum becomes sharper and moved to lower mS values whereas the minimum tends to disappear. These experimental trends are different from those of the enthalpy in agreement with the fact that heat capacity, being the derivative of enthalpy with respect to temperature, reflects additional terms generated by temperature change on the equilibria in solution. On the basis of a thermodynamic model recently proposed by us for properties first derivatives of Gibbs free energy, a quantitative treatment of the experimental data was done. Such an approach assumes that even in the dilute surfactant region monomers of surfactant associate with unimeric copolymer generating surfactant-copolymer aggregation complexes and, whenever the surfactant achieves the conditions for the micellization, the formation of copolymer-micelle mixed aggregates takes place. The equation derived for the heat capacity of transfer is more complex than that for the enthalpy because it contains five additional terms due to the shift of the equilibria induced by the temperature change. It turned out that these contributions, evaluated by using the equilibrium constants and the associated enthalpies, cannot be neglected for a quantitative treatment of the experimental data. The minimizing procedure provided the heat capacity changes for the formation of the surfactant-copolymer aggregation complexes and the copolymer-micelle mixed aggregates.