Nowadays the use of hydrogels for biomedical purposes is increasing because of their interesting features that allow the development of targeted drug delivery systems. Herein, hydrogel based on ...Laponite® (Lap) clay mineral as gelator and cucurbit6uril (CB6) molecules were synthetized for the delivery of flufenamic acid (FFA) for potential topical application. Firstly, the interaction between CB6 and FFA was assessed by UV‐vis spectroscopic measurements and molecular modeling calculations. Then, the obtained complex was used as filler for Lap hydrogel (Lap/CB6/FFA). The properties of the hydrogel in terms of viscosity and, self‐repair abilities were investigated; its morphology was imaged by scanning electron and polarized optical microscopies. Furthermore, the changes in the hydrodynamic radii and in the colloidal stability of CB6/Lap mixture were investigated in terms of translational diffusion from dynamic light scattering and ζ‐potential measurements. Finally, the kinetic in vitro release of FFA, from Lap/CB6/FFA hydrogel, was studied in a medium mimicking the pH of skin and the obtained results were discussed both by an experimental point of view and by molecular modeling calculations.
The use of hydrogels for biomedical purposes is increasing because of their interesting features that allow the development of targeted drug delivery systems. Herein, hydrogel based on Laponite® (Lap) clay mineral as gelator and cucurbit6uril (CB6) molecules were synthetized for the delivery of flufenamic acid (FFA) for potential topical application.
Invited for this month's cover are the collaborating groups of Prof. Serena Riela at University of Catania, Prof. César Viseras at University of Granada and Dr. Ignacio Sainz‐Diaz at Instituto ...Andaluz de Ciencias de la Tierra. The cover picture shows the possible application of the developed system. In particular, flufenamic acid, anti‐inflammatory and anti‐pyretic drug, was complexed into cucurbituril cavity and the supramolecular system obtained was used as filler for laponite® hydrogel for its topical delivery. More information can be found in the Research Article by Viseras‐Iborra, Riela, and co‐workers.
The use of hydrogels for biomedical purposes is increasing because of their interesting features that allow the development of targeted drug delivery systems. Herein, hydrogel based on Laponite® (Lap) clay mineral as gelator and cucurbit6uril (CB6) molecules were synthetized for the delivery of flufenamic acid (FFA) for potential topical application. Read more about the story behind the cover in the Cover Profile and about the research itself (DOI: 10.1002/cplu.202300370).
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•Polydioxanone in deep eutectic solvents has been spun via centrifugal spinning.•Polydioxanone microfibers as a rope or as a disk prove to possess suitable mechanical properties to be ...applied in skin tissue engineering.•Polydioxanone devices prove to be safe and effective to repair wound healing in an in vivo burn/excisional murine model.
Fiber spinning technologies attracted a great interest since the beginning of the last century. Among these, electrospinning is a widely diffuse technique; however, it presents some drawbacks such as low fiber yield, high energy demand and the use of organic solvents. On the contrary, centrifugal spinning is a more sustainable method and allows to obtain fiber using centrifugal force and melted materials. The aim of the present work was the design and the development of polydioxanone (PDO) microfibers intended for tissue engineering, using centrifugal spinning. PDO, a bioresorbable polymer currently used for sutures, was selected as low melting polyester and DES (deep eutectic solvents), either choline chloride/citric acid (ChCl/CA) or betaine/citric acid (Bet/CA) 1:1 M ratio, were used to improve PDO spinnability. Physical mixtures of DES and PDO were prepared using different weight ratios. These were then poured into the spinneret and melted at 140 °C for 5 min. After the complete melting, the blends were spun for 1 min at 700 rpm. The fibers were characterized for physico chemical properties (morphology; dimensions; chemical structure; thermal behavior; mechanical properties). Moreover, the preclinical investigation was performed in vitro (biocompatibility, adhesion and proliferation of fibroblasts) and in vivo (murine burn/excisional model to assess safety and efficacy). The multidisciplinary approach allowed to obtain an extensive characterization to develop PDO based microfibers as medical device for implant to treat full thickness skin wounds.
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Development of nanocomposite coating with antibiofilm properties is of fundamental importance to efficient fight biofilm formation preventing infections in biomedical area. In this ...context, halloysite nanotubes (HNTs), biocompatible and low-cost clay mineral, have been efficiently used as filler for different polymeric matrices affording several nanocomposites with appealing antimicrobial properties. The modification of HNTs surfaces represents a valuable strategy to improve the utilization of the clay for biological purposes. Experiments. Herein, the covalent modification of the HNTs lumen with properly designed dopamine derivatives with different perfluoroalkyl chain length is reported. The obtained nanomaterials are thoroughly characterized by several techniques. As proof of concept the antibiofilm properties on E. coli strain of the nanomaterials are assayed as well. Finally, the HNTs fillers were introduced into a polydopamine matrix allowing for the preparation of functional coatings, resistant to formation of microbial biofilms.
All characterization methods proved the selectivity of the modification and the increased hydrophobicity of the lumen. In particular 27Al solid state nuclear magnetic resonance (NMR) spectra showed a upfield shift of the Al signal. Studies on the antibiofilm properties highlighted different activities according to the length of perfluoroalkyl chains of organic molecules as proved by 19F solid state NMR spectra. The synthetized materials were promising for future application as coatings on medical implants.
The properties of montmorillonite (Mt) as a natural nanocarrier of drugs have been fully reported. Isoniazid (INH), a first-line tuberculostatic drug, was intercalated into this inorganic matrix and ...the equilibrium and thermodynamic aspects of the adsorption process were evaluated. Adsorption experiments were performed at different times and temperatures in aqueous medium. The overall adsorption process was the result of two simple processes: INH adsorption on the activated sites of Mt. followed by a slight precipitation phase of INH molecules over the adsorbed monolayer. Formation of the nanohybrid was spontaneous, exothermic and exoentropic, obtaining an increase in the thermodynamic stability of the system. The hybrid material (Mt-INH) was successfully prepared with high drug loading. Solid state characterization of the pure materials and the resulting nanohybrid was carried out. Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TGA), differential scanning calorimetry (DSC), surface charge, X-ray powder diffraction (XRPD) and high resolution transmission electron microscopy (HRTEM) coupled with energy dispersive spectroscopy (XEDS) and elemental X-ray maps served to correctly resolve the structure of the nanohybrid and to assess the nature and degree of the drug-clay interactions.
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•New nanohybrid montmorillonite/isoniazid was developed and fully characterized.•Kinetic and thermodynamic features of the adsorption process were determined.•The prepared montmorillonite/isoniazid nanohybrids could have potential application as modified drug delivery systems.
Recently, fluorescent sensors have gained considerable attention due to their high sensitivity, low cost and noninvasiveness. Among the different materials that can be used for this purpose, carbon ...dots (CDs) represent valuable candidates for applications in sensing. These, indeed, are easily synthesized, show high quantum yield and are highly biocompatible. However, it was pointed out that the photoluminescence properties of these nanomaterials are strictly dependent on the synthetic and purification methods adopted. The presence of halloysite nanotubes (HNTs), a natural, low cost and biocompatible clay mineral, has been found to be efficient in obtaining small and highly monodispersed CDs without long and tedious purification techniques. Herein, we report the comparison of synthetic pathways for obtaining halloysite-N-doped CDs (HNTs-NCDs) that could be used in biological sensing. One was based on the synthesis of N-doped CDs by a bottom-up approach on HNTs' surface by a MW pyrolysis process; the other one was based on the post-modification of pristine N-doped CDs with halloysite derivatives. The evaluation of the best synthetic route was performed by different physico-chemical techniques. It was found that the bottom-up approach led to the formation of N-doped CDs with different functional groups onto the HNTs' surface. This evidence was also translated in the different fluorescence quantum yields and the existence of several functional groups in the obtained materials was investigated by potentiometric titrations. Furthermore, the ability of the synthesized nanomaterials as sensors for Fe
ions detection was assessed by spectroscopic measurements, and the cellular uptake was verified by confocal/fluorescence microscopies as well.
The goal of this work is the design and the development of scaffolds based on maltodextrin (MD) to recover chronic lesions. MD was mixed with arginine/lysine/polylysine and the electrospinning was ...successfully used to prepare scaffolds with uniform and continuous nanofibers having regular shape and smooth surface. A thermal treatment was applied to obtain insoluble scaffolds in aqueous environment, taking the advantage of amino acids-polysaccharide conjugates formed via Maillard-type reaction. The morphological analysis showed that the scaffolds had nanofibrous structures, and that the cross-linking by heating did not significantly change the nanofibers' dimensions and did not alter the system stability. Moreover, the heating process caused a reduction of free amino group and proportionally increased scaffold cross-linking degree. The scaffolds were elastic and resistant to break, and possessed negative zeta potential in physiological fluids. These were characterized by direct antioxidant properties and Fe2+ chelation capability (indirect antioxidant properties). Moreover, the scaffolds were cytocompatible towards fibroblasts and monocytes-derived macrophages, and did not show any significant pro-inflammatory activity. Finally, those proved to accelerate the recovery of the burn/excisional wounds. Considering all the features, MD-poly/amino acids scaffolds could be considered as promising medical devices for the treatment of chronic wounds.
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•Nanofibrous scaffolds, based on maltodextrin and poly/amino acids have been prepared.•The scaffolds have been thermally cross-linked via Maillard-type reaction.•The scaffolds were biocompatible and characterized by antioxidant properties.•The scaffolds proved to restore skin integrity in an in vivo murine model.
In the last years, the use of clay minerals for pharmaceutical purposes has increased due to their interesting properties. Hectorite (Ht) is a clay belonging to the smectite group which has attracted ...attention for applications in biology, tissue engineering and as drug carrier and delivery system. However, the mechanisms involved in Ht cellular uptake and transport into cells, are still unclear. Herein, we used a labeled Ht (Ht/1Cl) to study both the cellular uptake, by confocal laser scanning microscopy, and internalization pathways involved in the cellular uptake, by various endocytosis-inhibiting studies and fluorescence microscopy. These studies highlighted that Ht can penetrate the cellular membrane, localizing mainly in the cytoplasm. The main intracellular transport mechanisms are the ATP-dependent ones and those where filaments and microtubules are involved. Finally, as proof of concept for the potential of Ht as carrier system, we envisaged the covalent grafting of the anticancer molecule methotrexate (MTX), chosen as model, to obtain the Ht-MTX nanomaterial. The covalent linkage was confirmed by several techniques and the morphology of the obtained nanomaterial was imaged by SEM and TEM investigations. The kinetic release of the drug from the Ht-MTX nanomaterial in physiological conditions was studied as well. Furthermore, cytotoxic studies on different cell lines, namely, HL-60, HL-60R, MCF-7, 5637, UMUC3 and RT112 showed that Ht could be a promising material for anticancer therapy.
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•Labeled Ht was used to study the cellular uptake and internalization pathways.•Ht can penetrate the cellular membrane, localizing mainly in the cytoplasm.•The main intracellular transport mechanisms are the ATP-dependent ones.•Mechanisms where filaments and microtubules are involved are also possible.•Ht was covalent modified with methotrexate for biological applications.
The prodrug approach, as well as the development of specific systems able to deliver a chemotherapeutic agent in the target site, decreasing the side effects often associated with its administration, ...are still a challenging. In this context, both methotrexate drug molecules (MTX) and biotin ligand moieties, whose receptors are overexpressed on the surface of several cancer cells, were loaded on halloysite nanotubes (HNTs) to develop nanomaterial based on multifunctional and “smart” delivery systems.
To highlight the crucial role played by biotin, carrier systems based on HNTs and MTX were also synthetized. In detail, several approaches were envisaged: i) a supramolecular interaction between the clay and the drug; ii) a covalent grafting of the drug onto the HNTs external surface and, iii) a combination of both approaches. The nanomaterials obtained were characterized by thermogravimetric analysis, FT-IR, and UV-vis spectroscopies, DLS and ζ−potential measurements and the morphologies were imaged by HAADF/STEM investigations. Kinetic release experiments at different pH conditions were also performed. Finally, as a proof-of-concept application of our pro-drug delivery systems based on HNTs in cancer therapy, the cytotoxic effects were evaluated on acute myeloid leukemia cell lines, HL60 and its multidrug resistance variant, HL60R. The obtained results showed that both the MTX prodrug system and the biotinylated ones played a crucial role in the biological activity and, they are promising agents for the cancer treatments.
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•Methotrexate (MTX) was both loaded and grafted on halloysite nanotubes (HNTs).•Different approaches allowed to obtained innovative HNTs based prodrugs.•An active targeting system based on biotin was also developed.•The nanomaterials showed enhanced antitumoral activity on two leukemia cell lines.
The design of multifunctional nanomaterials which can help the healing processes of skin, preventing the bacterial infections, is crucial for the development of suitable therapy for the treatment of ...chronic lesions. The use of clay minerals in wound healing applications is well documented since the prehistoric period and offers several advantages due to their intrinsic properties.
Herein, we report the development of ciprofloxacin carrier systems based on hectorite/halloysite (Ht/Hal) hybrid hydrogels for potential wound healing applications. To achieve this objective firstly the ciprofloxacin molecules were loaded onto Hal by a supramolecular and covalent approach. The so obtained fillers were thoroughly investigated by several techniques and at molecular level by means of quantum mechanics calculations along with empirical interatomic potentials. Afterwards the modified Hal were used as filler for Ht hydrogels. The introduction of modified Hal, in hectorite hydrogel, helps the gel formation with an improvement of the rheological properties. The in vitro kinetic release from both the fillers and from the hybrid hydrogels was studied both at skin's pH (5.4) and under neutral conditions (pH 7.4); in addition, the factors controlling the ciprofloxacin release process were determined and discussed. Finally, the in vitro biocompatibility of the Hal fillers was evaluated by means of cytotoxic assays and laser scanning confocal microscopy on normal human dermal fibroblasts.
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•Ciprofloxacin carrier systems based on Ht/Hal hybrid hydrogels were developed.•Ciprofloxacin molecules were loaded onto Hal filler by a supramolecular and covalent approach.•The introduction of modified Hal in Ht hydrogel improved rheological properties.•Kinetic release of the drug was studied both at skin's pH and under neutral conditions.•Biocompatibility of the Hal fillers was evaluated on normal human dermal fibroblasts.
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