Copper-Cystine Biohybrid-Embedded Nanofiber Aerogels Show Antibacterial and Angiogenic Properties.

Copper-cystine-based high aspect ratio structures (CuHARS) possess exceptional physical and chemical properties and exhibit remarkable biodegradability in human physiological conditions. Extensive testing has confirmed the biocompatibility and biodegradability of CuHARS under diverse biological conditions, making them a viable source of essential Cu2+. These ions are vital for catalyzing the production of nitric oxide (NO) from the decomposition of S-nitrosothiols (RSNOs) found in human blood. The ability of CuHARS to act as a Cu2+ donor under specific concentrations has been demonstrated in this study, resulting in the generation of elevated levels of NO. Consequently, this dual function makes CuHARS effective as both a bactericidal agent and a promoter of angiogenesis. In vitro experiments have shown that CuHARS actively promotes the migration and formation of complete lumens by redirecting microvascular endothelial cells. To maximize the benefits of CuHARS, they have been incorporated into biomimetic electrospun poly(ε-caprolactone)/gelatin nanofiber aerogels. Through the regulated release of Cu2+ and NO production, these channeled aerogels not only provide antibacterial support but also promote angiogenesis. Taken together, the inclusion of CuHARS in biomimetic scaffolds could hold great promise in revolutionizing tissue regeneration and wound healing.

Magnetite-sepiolite nanoarchitectonics for improving zein-based bionanocomposite foams.

Magnetic nanoarchitectures have been used to introduce multifunctionality in biopolymeric matrices. Bionanocomposite foams based on the corn protein zein were prepared for the first time using the hydrophobic properties of zein in a sequential treatment consisting of the removal of ethanol-soluble fractions, followed by the water swelling of the remaining phase and a further freeze-drying process. When this protocol is applied to zein pellets, they can be consolidated as porous monoliths. Moreover, it is possible to incorporate diverse types of inorganic nanoparticles in the starting pellet to produce the bionanocomposite foams. In particular, the preparation of superparamagnetic foams has been explored using two approaches: the direct incorporation of magnetite nanoparticles in a ferrofluid by impregnation in the foams, and the application of the foaming process to mixtures of zein with magnetite nanoparticles alone or previously assembled into sepiolite clay fibers. The first methodology leads to the production of inhomogeneous foams, while the use of magnetite nanoparticles and better Fe3O4-sepiolite nanoarchitectured materials as fillers results in more homogeneous materials with improved water stability and mechanical properties, offering superparamagnetic behavior. The resulting multifunctional foams have been tested in adsorption processes using the herbicide 4-chloro-2-methylphenoxyacetic acid as a model pollutant, confirming their potential utility in decontamination applications in open waters as they can be easily recovered from the aqueous medium using a magnet.

Effect of the combined addition of ultrasonicated kraft lignin and montmorillonite on hydroxypropyl methylcellulose bionanocomposites.

Although hydroxypropyl methylcellulose (HPMC) has been proposed as renewable substitute for traditional plastic, its barrier and active properties need to be improved. Thus, the combination of an organic residue such as kraft lignin (0-10% w/w) and a natural clay such as montmorillonite (3% w/w) by application of ultrasound can significantly improve HPMC properties. This is most likely due to the close interaction between lignin and montmorillonite, which leads to delamination of the clay and improves its dispersion within the HPMC matrix. Specifically, the addition of kraft lignin to the bionanocomposite films provided them with UV-shielding, antioxidant capacity and antibacterial activity. The incorporation of 3% montmorillonite resulted in reductions of 65.8% and 11.4% in oxygen (OP) and water vapor permeabilities (WVP), respectively. Moreover, a reduction of 43.8% in WVP was achieved when both lignin (1%) and montmorillonite (3%) were incorporated, observing a synergistic effect. Thus, the HPMC bionanocomposite with 1% lignin and 3% montmorillonite, presented good thermal stability and mechanical strength with significantly improved gas barrier permeability, as well as UV-shielding (maintaining a good transparency), antioxidant and antibacterial activities.

Cellulose/pectin-based materials incorporating Laponite-indole derivative hybrid for oral administration and controlled delivery of the neuroprotective drug.

Bionanocomposite materials based on clays have been designed for oral administration and controlled release of a neuroprotective drug derivative of 5-methylindole, which had featured an innovative pharmacological mechanism for the treatment of neurodegenerative diseases such as Alzheimer's. This drug was adsorbed in the commercially available Laponite® XLG (Lap). X-ray diffractograms confirmed its intercalation in the interlayer region of the clay. The loaded drug was 62.3 meq/100 g Lap, close to the cation exchange capacity of Lap. Per se toxicity studies and neuroprotective experiments versus the neurotoxin okadaic acid, a potent and selective inhibitor of protein phosphatase 2A (PP2A), confirmed that the clay-intercalated drug did not exert toxicity in cell cultures and provided neuroprotection. Release tests of the hybrid material performed in media mimicking the gastrointestinal tract indicated a drug release in acid medium close to 25 %. The hybrid was encapsulated in a micro/nanocellulose matrix and processed as microbeads, with pectin coating for additional protection, to minimize release under acidic conditions. Alternatively, low density materials based on a microcellulose/pectin matrix were evaluated as orodispersible foams showing fast disintegration times, sufficient mechanical resistance for handling, and release profiles in simulated media that confirmed a controlled release of the encapsulated neuroprotective drug.

Sepiolite-Hydrogels: Synthesis by Ultrasound Irradiation and Their Use for the Preparation of Functional Clay-Based Nanoarchitectured Materials.

Sepiolite and palygorskite fibrous clay minerals are 1D silicates featuring unique textural and structural characteristics useful in diverse applications, and in particular as rheological additives. Here we report on the ability of grinded sepiolite to generate highly viscous and stable hydrogels by sonomechanical irradiation (ultrasounds). Adequate drying of such hydrogels leads to low-density xerogels that show extensive fiber disaggregation compared to the starting sepiolite-whose fibers are agglomerated as bundles. Upon re-dispersion in water under high-speed shear, these xerogels show comparable rheological properties to commercially available defibrillated sepiolite products, resulting in high viscosity hydrogels that minimize syneresis. These colloidal systems are thus very interesting as they can be used to stabilize many diverse compounds as well as nano-/micro-particles, leading to the production of a large variety of composites and nano/micro-architectured solids. In this context, we report here various examples showing how colloidal routes based on sepiolite hydrogels can be used to obtain new heterostructured functional materials, based on their assembly to solids of diverse topology and composition such as 2D and 1D kaolinite and halloysite aluminosilicates, as well as to the 2D synthetic Mg,Al-layered double hydroxides (LDH).

Hydrophobic composite foams based on nanocellulose-sepiolite for oil sorption applications.

TEMPO (2,2,6,6-tetramethylpiperidin-1-oxyl)-oxidized cellulose nanofibers (CNF) were assembled to fibrous clay sepiolite (SEP) by means of a high shear homogenizer and an ultrasound treatment followed by lyophilization using three different methods: normal freezing, directional freezing, and a sequential combination of both methods. Methyltrimethoxysilane (MTMS) was grafted to the foam surface by the vapor deposition method to introduce hydrophobicity to the resulting materials. Both the SEP addition (for the normal and directional freezing methods) and the refreezing preparation procedure enhanced the compressive strength of the foams, showing compressive moduli in the range from 28 to 103 kPa for foams loaded with 20% w/w sepiolite. Mercury intrusion porosimetry shows that the average pore diameters were in the range of 30-45 µm depending on the freezing method. This large porosity leads to materials with very low apparent density, around 6 mg/cm3, and very high porosity >99.5%. In addition, water contact angle measurement and Fourier-transform infrared spectroscopy (FTIR) were applied to confirm the foam hydrophobicity, which is suitable for use as an oil sorbent. The sorption ability of these composite foams has been tested using olive and motor oils as models of organophilic liquid adsorbates, observing a maximum sorption capacity of 138 and 90 g/g, respectively.

Alginate bionanocomposite films containing sepiolite modified with polyphenols from myrtle berries extract.

Alginate nanocomposite films incorporating sepiolite (Sep) modified with myrtle berries extract (MBE) rich in polyphenols were prepared by solution casting method. The effects of different extract concentrations on the film properties were determined by measuring physicochemical, mechanical and antioxidant properties of the films. Fourier transform infrared (FTIR) spectra indicated that strong interactions between the polyphenols present in the MBE and sepiolite were involved in the films. The results suggested that incorporation of Sep-MBE hybrids into the films improved elongation at break, tensile strength, water vapor and UV barrier properties compared to the control film. The antioxidant activity of the films was significantly improved and raised with increasing content of MBE. The release kinetics results of MBE polyphenols from the active films into alcoholic food simulant indicated that the addition of Sep-MBE hybrids to alginate film is able to slow the release of MBE polyphenols. This study revealed the benefits of incorporation of Sep-MBE hybrids into the alginate films and their potential application as active packaging films or coating material.

Cellulose Nanofibers from a Dutch Elm Disease-Resistant Ulmus minor Clone.

The potential use of elm wood in lignocellulosic industries has been hindered by the Dutch elm disease (DED) pandemics, which have ravaged European and North American elm groves in the last century. However, the selection of DED-resistant cultivars paves the way for their use as feedstock in lignocellulosic biorefineries. Here, the production of cellulose nanofibers from the resistant Ulmus minor clone Ademuz was evaluated for the first time. Both mechanical (PFI refining) and chemical (TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical)-mediated oxidation) pretreatments were assessed prior to microfluidization, observing not only easier fibrillation but also better optical and barrier properties for elm nanopapers compared to eucalyptus ones (used as reference). Furthermore, mechanically pretreated samples showed higher strength for elm nanopapers. Although lower nanofibrillation yields were obtained by mechanical pretreatment, nanofibers showed higher thermal, mechanical and barrier properties, compared to TEMPO-oxidized nanofibers. Furthermore, lignin-containing elm nanofibers presented the most promising characteristics, with slightly lower transparencies.

Research and Patents on Coronavirus and COVID-19: A Review.

BACKGROUND: COVID-19 pandemic is a global problem that requires the point of view of basic sciences and medicine as well as social, economics and politics disciplines. Viral particles of coronaviruses including SARS-CoV-2 as well as other enveloped viruses like influenza virus could be considered as an approximation to functional core-shell nanoparticles and therefore, their study enters the realm of nanotechnology. In this context, nanotechnology can contribute to alleviate some of the current challenges posed by COVID-19 pandemic. METHODS: The present analysis contributed to diverse sources of general information, databases on scientific literature and patents to produce a review affording information on relevant areas where as nanotechnology has offered response to coronavirus challenges in the past and may be relevant now, and has offered an update of the current information on SARS-CoV-2 and COVID-19 issues. RESULTS: This review contribution includes specific information including: 1) An introduction to current research on nanotechnology and related recent patents for COVID-19 responses; 2) Analysis of nonimmunogenic and immunogenic prophylaxis of COVID-19 using Nanotechnology; 3) Tools devoted to detection & diagnosis of coronaviruses and COVID-19: the role of Nanotechnology; and 4) A compilation on the research and patents on nanotechnology dealing with therapeutics & treatments of COVID-19. CONCLUSION: Among the increasing literature on COVID-19, there are few works analyzing the relevance of Nanotechnology, and giving an analysis on patents dealing with coronaviruses that may provide useful information on the area. This review offers a general view of the current research investigation and recent patents dealing with aspects of immunogenic and non-immunogenic prophylaxis, detection and diagnosis as well as therapeutics and treatments.

Nanotechnology Responses to COVID-19.

Researchers, engineers, and medical doctors are made aware of the severity of the COVID-19 infection and act quickly against the coronavirus SARS-CoV-2 using a large variety of tools. In this review, a panoply of nanoscience and nanotechnology approaches show how these disciplines can help the medical, technical, and scientific communities to fight the pandemic, highlighting the development of nanomaterials for detection, sanitation, therapies, and vaccines. SARS-CoV-2, which can be regarded as a functional core-shell nanoparticle (NP), can interact with diverse materials in its vicinity and remains attached for variable times while preserving its bioactivity. These studies are critical for the appropriate use of controlled disinfection systems. Other nanotechnological approaches are also decisive for the development of improved novel testing and diagnosis kits of coronavirus that are urgently required. Therapeutics are based on nanotechnology strategies as well and focus on antiviral drug design and on new nanoarchitectured vaccines. A brief overview on patented work is presented that emphasizes nanotechnology applied to coronaviruses. Finally, some comments are made on patents of the initial technological responses to COVID-19 that have already been put in practice.

Zein-layered hydroxide biohybrids: strategies of synthesis and characterization.

This work constitutes a basic study about the first exploration on the preparation of biohybrids based on the corn protein zein and layered metal hydroxides, such as layered double hydroxides (LDH) and layered single hydroxides (LSHs). For this purpose, MgAl layered double hydroxide and the Co2(OH)3 layered single hydroxide were selected as hosts, and various synthetic approaches were explored to achieve the formation of the zein-layered hydroxide biohybrids, profiting from the presence of negatively charged groups in zein in basic medium. Zein-based layered hydroxide biohybrids were characterized by diverse physicochemical techniques such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis/differential thermal analysis (TG/DTA), solid state 13C cross-polarization magical angle spinning nuclear magnetic resonance (CP-MAS NMR), field emission-scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), etc., which suggest that the different synthesis procedures employed and the anion located in the interlayer region of the inorganic host material seem to have a strong influence on the final features of the biohybrids, resulting in mixed, single intercalated, or highly exfoliated intercalated phases. Thus, the resulting biohybrids based on zein and layered hydroxides could have interest in applications in biomedicine, biosensing, materials for electronic devices, catalysis, and photocatalysis.

Cellulose-based biomaterials integrated with copper-cystine hybrid structures as catalysts for nitric oxide generation.

Bionanocomposite materials were developed from the assembly of polymer-coated copper-cystine high-aspect ratio structures (CuHARS) and cellulose fibers. The coating of the metal-organic materials with polyallylamine hydrochloride (PAH) allows their covalent linkage to TEMPO-oxidized cellulose by means of EDC/NHS. The resulting materials can be processed as films or macroporous foams by solvent casting and lyophilization, respectively. The films show good mechanical behavior with Young's moduli around 1.5 GPa as well as resistance in water, while the obtained foams show an open network of interconnected macropores with average diameters around 130 µm, depending on the concentration of the initial suspension, and compression modulus values around 450 kPa, similar to other reported freeze-dried nanocellulose-based aerogels. Based on these characteristics, the cellulose/PAH-CuHARS composites are promising for potential biomedical applications as implants or wound dressing materials. They have proved to be effective in the decomposition of low molecular weight S-nitrosothiols (RSNOs), similar to those existing in blood, releasing nitric oxide (NO). This effect is attributed to the presence of copper in the crystalline structure of the CuHARS building unit, which can be gradually released in the presence of redox species like ascorbic acid, typically found in blood. The resulting biomaterials can offer the interesting properties associated with NO, like antimicrobial activity as preliminary tests showed here with Escherichia coli and Staphylococcus epidermidis. In the presence of physiological concentration of RSNOs the amount of generated NO (around 360 nM) is not enough to show bactericidal effect on the studied bacteria, but it could provide other properties inherent to NO even at low concentration in the nM range like anti-inflammatory and anti-thrombotic effects. The cytotoxic effect recorded of the films on rat brain endothelial cells (BMVECs) is least significant and proves them to be friendly enough for further biological studies.

Layered double hydroxide/sepiolite hybrid nanoarchitectures for the controlled release of herbicides.

In this work, organic-inorganic hybrid nanoarchitectures were prepared in a single coprecipitation step by assembling magnesium-aluminum layered double hydroxides (MgAl-LDH) and a sepiolite fibrous clay, with the simultaneous encapsulation of the herbicide 2-methyl-4-chlorophenoxyacetic acid (MCPA) as the MgAl-LDH retains its ion exchange properties. The synthetic procedure was advantageous in comparison to the incorporation of MCPA by ion exchange after the formation of the LDH/sepiolite nanoarchitecture in a previous step, as it was less time consuming and gave rise to a higher loading of MCPA. The resulting MCPA-LDH/sepiolite nanoarchitectures were characterized by various physicochemical techniques (XRD, FTIR and 29Si NMR spectroscopies, CHN analysis and SEM) that revealed interactions of LDH with the sepiolite fibers through the silanol groups present on the outer surface of sepiolite, together with the intercalation of MCPA in the LDH confirmed by the increase in the basal spacing from 0.77 nm for the pristine LDH to 2.32 nm for the prepared materials. The amount of herbicide incorporated in the hybrid nanoarchitectures prepared by the single-step coprecipitation method surpassed the CEC of LDH (ca. 330 mEq/100 g), with values reaching 445 mEq/100 g LDH for certain compositions. This suggests a synergy between the inorganic solids that allows the nanoarchitecture to exhibit better adsorption properties than the separate components. Additionally, in the release assays, the herbicide incorporated in the hybrid nanoarchitectures could be completely released, which confirms its suitability for agricultural applications. In order to achieve a more controlled release of the herbicide and to act for several days on the surface of the soil, the hybrid nanoarchitectures were encapsulated in a biopolymer matrix of alginate/zein and shaped into spheres. In in vitro tests carried out in bidistilled water, a continuous release of MCPA from the bionanocomposite beads was achieved for more than a week, while the non-encapsulated materials released the 100% of MCPA in 48 h. Besides, the encapsulation may allow for better handling and transport of the herbicide.

Integration of a Copper-Containing Biohybrid (CuHARS) with Cellulose for Subsequent Degradation and Biomedical Control.

We previously described the novel synthesis of a copper high-aspect ratio structure (CuHARS) biohybrid material using cystine. While extremely stable in water, CuHARS is completely (but slowly) degradable in cellular media. Here, integration of the CuHARS into cellulose matrices was carried out to provide added control for CuHARS degradation. Synthesized CuHARS was concentrated by centrifugation and then dried. The weighed mass was re-suspended in water. CuHARS was stable in water for months without degradation. In contrast, 25 μg/mL of the CuHARS in complete cell culture media was completely degraded (slowly) in 18 days under physiological conditions. Stable integration of CuHARS into cellulose matrices was achieved through assembly by mixing cellulose micro- and nano-fibers and CuHARS in an aqueous (pulp mixture) phase, followed by drying. Additional materials were integrated to make the hybrids magnetically susceptible. The cellulose-CuHARS composite films could be transferred, weighed, and cut into usable pieces; they maintained their form after rehydration in water for at least 7 days and were compatible with cell culture studies using brain tumor (glioma) cells. These studies demonstrate utility of a CuHARS-cellulose biohybrid for applied applications including: (1) a platform for biomedical tracking and (2) integration into a 2D/3D matrix using natural products (cellulose).

Intercalation of metformin into montmorillonite.

Metformin hydrochloride is an extensively used antidiabetic drug that according to the results reported here is able to spontaneously intercalate layered silicates like the montmorillonite clay mineral following an ion-exchange mechanism. The adsorption isotherm from water solutions shows a great affinity of metformin towards the clay mineral, which can retain about thrice the exchange capacity of the clay. The adsorbed excess was easily removed by washing with water, leading to an intercalation compound that contains 93 meq of metformin per 100 g of montmorillonite, matching the CEC value of this clay. The intercalated metformin is arranged in the interlayer space as a monolayer of monoprotonated molecules, which remain strongly entrapped within the solid. These new hybrid materials were characterized by elemental chemical analysis, XRD, FTIR, TG-DTA, and NMR. We preliminary evaluated the use of the metformin-montmorillonite intercalation compound as a drug delivery system, determining the liberation kinetics of metformin at diverse pH values that mimic the gastrointestinal tract. Although the release rate was not totally slowed down, the system seems promising in view of further optimization for drug delivery applications.

Building Up Functional Bionanocomposites from the Assembly of Clays and Biopolymers.

Functional bionanocomposites are developed from the assembly of naturally occurring polymers and inorganic solids that show at least one dimension at the nanoscale. Our research group focused on the development of bionanocomposites based on clay minerals, including smectites and fibrous silicates, as well as layered double hydroxides. The resulting materials show interesting properties regarding biocompatibility and biodegradability, together with improved mechanical and thermal properties in comparison to the pristine biopolymer. Besides these characteristics, they offer also other interesting functional properties that allow their potential use in a wide range of applications, including sensors, drug delivery and other health care applications, bioplastics and environmental remediation. For these materials, nature provides not only the components but also the inspiration to develop new combinations that may give rise to nanostructured biomaterials with exceptional features.

Functional Carboxymethylcellulose/Zein Bionanocomposite Films Based on Neomycin Supported on Sepiolite or Montmorillonite Clays.

The present work introduces new functional bionanocomposite materials based on layered montmorillonite and fibrous sepiolite clays and two biopolymers (carboxymethylcellulose polysaccharide and zein protein) to produce drug-loaded bionanocomposite films for antibiotic topical delivery. Neomycin, an antibiotic indicated for wound infections, was employed as the model drug in this study. The physical properties and the antimicrobial activity of these materials were evaluated as a function of the type of hybrid and the amount of zein protein incorporated in the bionanocomposite films. In addition, the interfacial and physicochemical properties of these new clay-drug hybrids have been studied through a combination of experimental and computational methodologies, where the computational studies confirm the intercalation of neomycin into the montmorillonite layers and the possible penetration of the drug in the tunnels of sepiolite, as pointed out by N2 adsorption and X-ray diffraction techniques. The antimicrobial activity of these bionanocomposite materials show that the films based on montmorillonite-neomycin display a more pronounced inhibitory effect of the bacterial growth than those prepared with the sepiolite-neomycin hybrid. Such effect can be related to the difficult release of neomycin adsorbed on sepiolite due to a strong interaction between both components.

Bionanocomposite foams based on the assembly of starch and alginate with sepiolite fibrous clay.

Bionanocomposite foams based on alginate, potato starch and the microfibrous clay mineral sepiolite as reinforcing filler were prepared by lyophilization. Spectroscopic techniques were applied in order to assess the interaction mechanism established between the inorganic fibers and the polysaccharide chains, which is established between the hydroxyl groups in the polysaccharide chains and the silanol groups at the external surface of the sepiolite fibers. The textural properties studied by means of mercury intrusion porosimetry, FE-SEM and X-ray microtomography, revealed a decrease in porosity as the sepiolite content increased. Mechanical properties were also determined for the studied foams, showing an increase in compression moduli from 7.3MPa in the foam without sepiolite to 29MPa in foams containing 10% starch, 40% sepiolite and 50% alginate. Horizontal burning tests were carried out for a preliminary evaluation of the role of the inorganic fibers on the fire resistance properties of the bionanocomposite foams, revealing that bionanocomposite foams with sepiolite content >25% behave as auto-extinguishable materials. Post-synthesis cross-linking with CaCl2 was carried out in some of these samples, leading to an increase in the compression modulus up to 40MPa for the optimal composition.

Effective intercalation of zein into Na-montmorillonite: role of the protein components and use of the developed biointerfaces.

Biohybrid materials based on the intercalation of zein, the major storage protein in corn, into sodium-exchanged montmorillonite were prepared following two synthesis strategies. The first one made use of zein dissolved in 80% (v/v) ethanol/water solution, the usual solvent for this protein, while the second method is new and uses a sequential process that implies the previous separation of zein components in absolute ethanol. This treatment of zein with ethanol renders a soluble yellow phase and an agglomerate of insoluble components, which are able to intercalate the layered silicate when an aqueous dispersion of montmorillonite is added to the ethanol medium containing both phases. The diverse steps in this second route were investigated individually in order to understand the underlying mechanism that drives to the intercalation of this complex hydrophobic biomacromolecule into the hydrophilic interlayer space of sodium-exchanged montmorillonite. In addition to physicochemical characterization of the resulting materials, these biohybrid interfaces were also evaluated as biofillers in the preparation of diverse ecofriendly nanocomposites.

Bionanocomposites containing magnetic graphite as potential systems for drug delivery.

New magnetic bio-hybrid matrices for potential application in drug delivery are developed from the assembly of the biopolymer alginate and magnetic graphite nanoparticles. Ibuprofen (IBU) intercalated in a Mg-Al layered double hydroxide (LDH) was chosen as a model drug delivery system (DDS) to be incorporated as third component of the magnetic bionanocomposite DDS. For comparative purposes DDS based on the incorporation of pure IBU in the magnetic bio-hybrid matrices were also studied. All the resulting magnetic bionanocomposites were processed as beads and films and characterized by different techniques with the aim to elucidate the role of the magnetic graphite on the systems, as well as that of the inorganic brucite-like layers in the drug-loaded LDH. In this way, the influence of both inorganic components on the mechanical properties, the water uptake ability, and the kinetics of the drug release from these magnetic systems were determined. In addition, the possibility of modulating the levels of IBU release by stimulating the bionanocomposites with an external magnetic field was also evaluated in in vitro assays.