Research Article Cite This: ACS Appl. Mater. Interfaces 2018, 10, 8265−8273
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Nanohydrogel Formation within the Halloysite Lumen for Triggered and Sustained Release Giuseppe Cavallaro,† Giuseppe Lazzara,*,† Stefana Milioto,† Filippo Parisi,† Vladimir Evtugyn,‡ Elvira Rozhina,‡ and Rawil Fakhrullin*,‡ †
Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, Viale delle Scienze, pad. 17, 90128 Palermo, Italy Institute of Fundamental Biology and Medicine, Kazan Federal University, Kreml Uramı 18, Kazan, Republic of Tatarstan 420008, Russian Federation
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S Supporting Information *
ABSTRACT: An easy strategy to obtain nanohydrogels within the halloysite nanotube (HNTs) lumen was investigated. Inorganic reverse micelles based on HNTs and hexadecyltrimethylammonium bromides were dispersed in chloroform, and the hydrophilic cavity was used as a nanoreactor to confine the gel formation based on alginate cross-linked by calcium ions. Spectroscopy and electron microscopy experiments proved the confinement of the polymer into the HNT lumen and the formation of calciummediated networks. Biological tests proved the biocompatibility of the hybrid hydrogel. The nanogel in HNTs was suitable for drug loading and sustained release with the opportunity of triggered burst release by chemical stimuli. Here, we propose a new strategy based on inorganic reverse micelles for nanohydrogel formation, which are suitable for industrial and biological applications as well as for selective and triggered adsorption and/or release. KEYWORDS: halloysite, inorganic reverse micelles, nanohydrogel, sustained release, alginate
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sis,21,22 nanocomposite packaging,23−26 and pharmaceutical applications.27−30 HNTs are obtained from natural sources with a polydisperse size; their length is in the micrometers range, whereas their external and internal diameters range between 50−80 and 10−15 nm.31,32 Although its chemical composition is dependent on the deposit,33 halloysite has a unit cell formed by Al2Si2O5(OH)4·2H2O, where the Al is disposed in a gibbsite octahedral sheet (Al−OH) at the inner surface and siloxane (Si−O−Si) groups are exposed at the external surface. HNTs dispersed in water in a wide pH interval (from 3 to 8) show a charge separation and therefore a positively charged lumen and a negative charge at the outer surface, which dominates the net nanotube charge value.31 Such a peculiarity not only influences the liquid crystalline and assembling behavior of aqueous halloysite dispersions34,35 but also allows for the selective modification of HNT surfaces by ion exchange.36−38 The selective adsorption of sodium alkanoates and sodium dodecyl sulfate onto the HNT lumen generates tubular inorganic micelles with efficient solubilization ability toward hydrophobic molecules.16,39 Dioctyl sulfosuccinate sodium salts are effective in stabilizing oil-in-water Pickering emulsions.40 Covalent modification of the HNT lumen to enhance the loading
INTRODUCTION Nanotechnology-based delivery systems offer interesting alternative ways of administration to improve patient compliance and to target delivery at the proper site. Novel micro-/nanohydrogel-based formulations for delivering molecular therapeutics have attracted scientific interests.1 Inverse microemulsion is a well-established method to obtain the confinement of water for controlled nanoparticle synthesis2,3 or micro-/nanohydrogel preparation in a variety of sizes.4 Reducing the size of gel matrixes improves their response time to external physicochemical stimuli in comparison with the bulk counterparts. The literature reports that nanohydrogels, nanogels, or microgels are promising in sustained drug delivery.5−9 One major limitation of nanohydrogels for clinical applications is their structural instability for the precise control of the release of drugs during the treatment protocol. To overcome these limitations, montmorillonite nanocomposite hydrogels were proposed as they possess interesting antifatigue and delivery properties.10 Among clays, halloysite nanotubes (HNTs) are very promising because of their versatile properties, such as hollow tubular morphology, tunable surface chemistry, and biocompatibility.11 Tests demonstrated the low toxicity of halloysite toward micro-organisms12,13 and nematodes.14 These features make HNTs suitable for development of hybrid nanomaterials for wastewater remediation,15−18 smart coating,19,20 cataly© 2018 American Chemical Society
Received: December 20, 2017 Accepted: February 12, 2018 Published: February 12, 2018 8265
DOI: 10.1021/acsami.7b19361 ACS Appl. Mater. Interfaces 2018, 10, 8265−8273
Research Article
ACS Applied Materials & Interfaces
Methods. Thermogravimetric analyses were performed by using a Q5000 IR apparatus (TA Instruments) under a nitrogen flow of 25 cm3 min−1 for the sample and 10 cm3 min−1 for the balance. The explored temperature interval ranged between 25 and 900 °C at a heating rate of 20 °C min−1. Dynamic light scattering (DLS) and ζpotential measurements were carried out by means of a Zetasizer Nano-ZS (Malvern Instruments) at 25.0 ± 0.1 °C. The field-time autocorrelation functions were analyzed by ILT. A wavelength of 632.8 nm and a scattering angle of 173° were used. DLS experiments were conducted in chloroform dispersions with variable concentrations (see the Supporting Information). Fourier transform infrared (FTIR) spectra were determined at room temperature using a Frontier FTIR spectrometer (PerkinElmer) in KBr. The spectral resolution was 2 cm−1. The steady-state fluorescence spectra for alginate labeled with fluorescein were registered with a FluoroMax 4 (Jobin-Yvon) spectrofluorometer (right angle geometry, 1 cm × 1 cm quartz cell) at 25.0 ± 0.1 °C. The excitation wavelength was of 470 nm, and the emission spectra were recorded from 500 to 680 nm. The widths of slits were set at 1.5 and 1.5 nm for excitation and emission, respectively. UV−vis spectra of doxycycline chlorhydrate were recorded by a SPECORD S600 Analytik Jena. Doxycycline chlorhydrate in water presents a peak at 362 nm with an extinction coefficient of 23.6 ± 0.3 cm2 mg−1. For transmission electron microscopy (TEM) imaging, a Hitachi HT7700 EXALENS transmission electron microscope was used. A droplet of the suspension (10 μL) was placed on a carbon lacey 3 mm copper grid and then dried at room temperature. TEM imaging was performed at a 100 kV accelerating voltage. Energy-dispersive X-ray (EDX) analysis was carried out in the STEM mode using an Oxford Instruments X-Max 80 T detector. The surface morphology of the prepared materials was studied by using a microscope ESEM FEI Quanta 200F. Before each scanning electron microscopy (SEM) experiment, the surface of the sample was coated with gold in argon by means of an Edwards sputter coater S150A to avoid charging under electron beam. The measurements were carried out in the high vacuum mode (
