Thermosensitive Polyurethane-Based Hydrogels as Potential Vehicles for Meloxicam Delivery.

Meloxicam (MX) is a nonsteroidal anti-inflammatory drug (NSAID) used mainly to reduce pain, inflammation, and fever. In the present study, thermosensitive polyurethane (PU)-based hydrogels with various excipients (PEG, PVP, HPC, and essential oil) were prepared and loaded with MX. Rheological investigations were carried out on the PU-based formulations in various shear regimes, and their viscoelastic characteristics were determined. The average size of the PU micelles was 35.8 nm at 37 °C and slightly increased at 37 nm in the presence of MX. The zeta potential values of the hydrogels were between -10 mV and -11.5 mV. At pH = 6 and temperature of 37 °C, the formulated PU-based hydrogels loaded with MX could deliver significant amounts of the active substance, between 60% and 80% over 24-48 h and more than 90% within 2 weeks. It was found that anomalous transport phenomena dominated MX's release mechanism from the PU-based networks. The results are encouraging for further studies aiming to design alternative carriers to commercial dosage forms of nonsteroidal anti-inflammatory drugs.

Influence of ZnO Nanoparticles on the Properties of Ibuprofen-Loaded Alginate-Based Biocomposite Hydrogels with Potential Antimicrobial and Anti-Inflammatory Effects.

Hydrogels are a favorable alternative to accelerate the burn wound healing process and skin regeneration owing to their capability of absorbing contaminated exudates. The bacterial infections that occur in burn wounds might be treated using different topically applied materials, but bacterial resistance to antibiotics has become a major problem worldwide. Therefore, the use of non-antibiotic treatments represents a major interest in current research. In this study, new antibiocomposite hydrogels with anti-inflammatory and antimicrobial properties based on hyaluronic acid (HA) and sodium alginate (AG) were obtained using 4-(4,6-dimethoxy-1,3,5-triazinyl-2)-4-methylmorpholinium chloride as an activator. The combination of Ibuprofen, a non-steroidal anti-inflammatory drug commonly used to reduce inflammation, fever and pain in the body, with zinc oxide nanoparticles (ZnO NPs) was used in this study aimed at creating a complex hydrogel with anti-inflammatory and antimicrobial action and capable of improving the healing process of wounds caused by burns. FTIR spectra confirmed the cross-linking of AG with HA as well as the successful incorporation of ZnO NPs. Using electronic microscopy, it was noticed that the morphology of hydrogels is influenced by the incorporation of ZnO nanoparticles. Moreover, the incorporation of ZnO nanoparticles into hydrogels also has an influence on the swelling behavior at both pH 7.4 and 5.4. In fact, the swelling rate is lower when the amounts of the activator, HA and ZnO NPs are high. A drug release rate of almost 100% was observed for hydrogels without ZnO NPs, whereas the addition of nanoparticles to hydrogels led to a decrease in the release rate to 68% during 24 h. Cellular viability tests demonstrated the non-cytotoxic behavior of the hydrogels without the ZnO NPs, whereas a weak to moderate cytotoxic effect was noticed for hydrogels with ZnO NPs. The hydrogels containing 4% and 5% ZnO NPs, respectively, showed good antimicrobial activity against the S. aureus strain. These preliminary data prove that these types of hydrogels can be of interest as biomaterials for the treatment of burn wounds.

Self-Healing of Pluronic® F127 Hydrogels in the Presence of Various Polysaccharides.

Thermoresponsive Pluronic® F127 (PL) gels in water were investigated through rheological tests in different shear conditions. The gel strength was tuned with the addition of 1% polysaccharide solution. In the presence of xanthan gum (XG), the viscoelastic behavior of PL-based hydrogels was improved in aqueous environment, but the rheological behavior was less changed with the addition of XG in PBS solutions, whereas in the presence of 0.1 M NaCl, the viscoelastic parameters decreased. PL micellar networks exhibited a self-healing ability, recovering their initial structure after applying cycles of high strain. The rheological characteristics of the PL hydrogel changed with the addition of 1% polysaccharides (xanthan gum, alginate, κ-carrageenan, gellan, or chitosan). PL/polysaccharide systems form temperature-responsive hydrogels with shear thinning behavior, yield stress, and self-healing ability, being considered a versatile platform for injectable biomaterials or bioinks. Thus, in the presence of xanthan gum in aqueous medium, the gel strength was improved after applying a high strain (the values of elastic modulus increased). The other investigated natural polymers induced specific self-healing behaviors. Good performances were observed with the addition of gellan gum, alginate, and κ-carrageenan, but for high values of strain, the ability to recover the initial structure decreased. A modest self-healing behavior was observed in the presence of chitosan and xanthan gum dissolved in NaCl solution.

Poly(vinyl alcohol)/Pullulan Composite Hydrogels as a Potential Platform for Wound Dressing Applications.

Hydrogels are 3D networks with an excellent ability to retain a high amount of water or biological fluids, representing suitable candidates for wound dressing applications. They can provide a protective barrier and a moist environment, facilitating wound treatment. The present paper focuses on physical hydrogels obtained from poly(vinyl alcohol) (PVA) and pullulan (PULL) mixtures in different weight ratios by using the freezing/thawing method. Hybrid hydrogels of similar polymer compositions were prepared in the presence of 0.5% Laponite® RD. The influence of polysaccharide and clay addition on the properties of PVA hydrogels was investigated. Scanning electron microscopy showed evidence of the inner porous structure. The viscoelastic properties were investigated in different shear conditions and revealed the influence of the hydrogel composition on the network strength. The swelling behavior was followed in physiological saline solutions at 37 °C and pH = 7.4. For all samples, a quasi-Fickian diffusion mechanism was found. The delivery of neomycin sulfate was studied in similar conditions as for the swelling tests (0.15 M NaCl solutions; 37 °C; pH = 7.4) and different kinetic models were used to determine the release mechanism. The Peppas-Sahlin approach described very well the in vitro drug release mechanism from the polymeric hydrogels in the absence of clay. However, the hybrid polymer/clay hydrogels showed the best fit with the Korsmeyer-Peppas model. According to the present study, the porous membranes containing 40-60% PULL (in absence of clay) are suitable for the release of therapeutic agents at wound sites in physiological conditions.

Diversity of Bioinspired Hydrogels: From Structure to Applications.

Hydrogels are three-dimensional networks with a variety of structures and functions that have a remarkable ability to absorb huge amounts of water or biological fluids. They can incorporate active compounds and release them in a controlled manner. Hydrogels can also be designed to be sensitive to external stimuli: temperature, pH, ionic strength, electrical or magnetic stimuli, specific molecules, etc. Alternative methods for the development of various hydrogels have been outlined in the literature over time. Some hydrogels are toxic and therefore are avoided when obtaining biomaterials, pharmaceuticals, or therapeutic products. Nature is a permanent source of inspiration for new structures and new functionalities of more and more competitive materials. Natural compounds present a series of physico-chemical and biological characteristics suitable for biomaterials, such as biocompatibility, antimicrobial properties, biodegradability, and nontoxicity. Thus, they can generate microenvironments comparable to the intracellular or extracellular matrices in the human body. This paper discusses the main advantages of the presence of biomolecules (polysaccharides, proteins, and polypeptides) in hydrogels. Structural aspects induced by natural compounds and their specific properties are emphasized. The most suitable applications will be highlighted, including drug delivery, self-healing materials for regenerative medicine, cell culture, wound dressings, 3D bioprinting, foods, etc.

Chitosan Membranes Containing Plant Extracts: Preparation, Characterization and Antimicrobial Properties.

The main strategy of this study was to combine the traditional perspective of using medicinal extracts with polymeric scaffolds manufactured by an engineering approach to fabricate a potential dressing product with antimicrobial properties. Thus, chitosan-based membranes containing S. officinalis and H. perforatum extracts were developed and their suitability as novel dressing materials was investigated. The morphology of the chitosan-based films was assessed by scanning electron microscopy (SEM) and the chemical structure characterization was performed via Fourier transform infrared spectroscopy (FTIR). The addition of the plant extracts increased the sorption capacity of the studied fluids, mainly at the membrane with S. officinalis extract. The membranes with 4% chitosan embedded with both plant extracts maintained their integrity after being immersed for 14 days in incubation media, especially in PBS. The antibacterial activities were determined by the modified Kirby-Bauer disk diffusion method for Gram-positive (S. aureus ATCC 25923, MRSA ATCC 43300) and Gram-negative (E. coli ATCC 25922, P. aeruginosa ATCC 27853) microorganisms. The antibacterial property was enhanced by incorporating the plant extracts into chitosan films. The outcome of the study reveals that the obtained chitosan-based membranes are promising candidates to be used as a wound dressing due to their good physico-chemical and antimicrobial properties.

Development of Polyurethane/Peptide-Based Carriers with Self-Healing Properties.

In situ-forming gels with self-assembling and self-healing properties are materials of high interest for various biomedical applications, especially for drug delivery systems and tissue regeneration. The main goal of this research was the development of an innovative gel carrier based on dynamic inter- and intramolecular interactions between amphiphilic polyurethane and peptide structures. The polyurethane architecture was adapted to achieve the desired amphiphilicity for self-assembly into an aqueous solution and to facilitate an array of connections with peptides through physical interactions, such as hydrophobic interactions, dipole-dipole, electrostatic, π-π stacking, or hydrogen bonds. The mechanism of the gelation process and the macromolecular conformation in water were evaluated with DLS, ATR-FTIR, and rheological measurements at room and body temperatures. The DLS measurements revealed a bimodal distribution of small (~30-40 nm) and large (~300-400 nm) hydrodynamic diameters of micelles/aggregates at 25 °C for all samples. The increase in the peptide content led to a monomodal distribution of the peaks at 37 °C (~25 nm for the sample with the highest content of peptide). The sol-gel transition occurs very quickly for all samples (within 20-30 s), but the equilibrium state of the gel structure is reached after 1 h in absence of peptide and required more time as the content of peptide increases. Moreover, this system presented self-healing properties, as was revealed by rheological measurements. In the presence of peptide, the structure recovery after each cycle of deformation is a time-dependent process, the recovery is complete after about 300 s. Thus, the addition of the peptide enhanced the polymer chain entanglement through intermolecular interactions, leading to the preparation of a well-defined gel carrier. Undoubtedly, this type of polyurethane/peptide-based carrier, displaying a sol-gel transition at a biologically relevant temperature and enhanced viscoelastic properties, is of great interest in the development of medical devices for minimally invasive procedures or precision medicine.

Hybrid Hydrogels for Neomycin Delivery: Synergistic Effects of Natural/Synthetic Polymers and Proteins.

This paper reports new physical hydrogels obtained by the freezing/thawing method. They include pullulan (PULL) and poly(vinyl alcohol) (PVA) as polymers, bovine serum albumin (BSA) as protein, and a tripeptide, reduced glutathione (GSH). In addition, a sample containing PULL/PVA and lysozyme was obtained in similar conditions. SEM analysis evidenced the formation of networks with porous structure. The average pore size was found to be between 15.7 µm and 24.5 µm. All samples exhibited viscoelastic behavior typical to networks, the hydrogel strength being influenced by the protein content. Infrared spectroscopy analysis revealed the presence of intermolecular hydrogen bonds and hydrophobic interactions (more pronounced for BSA content between 30% and 70%). The swelling kinetics investigated in buffer solution (pH = 7.4) at 37 °C evidenced a quasi-Fickian diffusion for all samples. The hydrogels were loaded with neomycin trisulfate salt hydrate (taken as a model drug), and the optimum formulations (samples containing 10-30% BSA or 2% lysozyme) proved a sustained drug release over 480 min in simulated physiological conditions. The experimental data were analyzed using different kinetic models in order to investigate the drug release mechanism. Among them, the semi-empirical Korsmeyer-Peppas and Peppas-Sahlin models were suitable to describe in vitro drug release mechanism of neomycin sulfate from the investigated hybrid hydrogels. The structural, viscoelastic, and swelling properties of PULL/PVA/protein hybrid hydrogels are influenced by their composition and preparation conditions, and they represent important factors for in vitro drug release behavior.

The Development and Study of Some Composite Membranes Based on Polyurethanes and Iron Oxide Nanoparticles.

To improve the performance of composite membranes, their morphology can be tailored by precise control of the fabrication methods and processing conditions. To this end, the aim of this study was to develop novel high-performance composite membranes based on polyurethane matrix and magnetic nanoparticles with the desired morphology and stability, by selecting the proper method and fabrication systems. These well-prepared composite membranes were investigated from the point of view of their morphological, physico-chemical, mechanical, dielectric, and magnetic properties. In addition, their in vitro cytocompatibility was also verified by the MTT assay and their cell morphology. The results of this study can provide valuable information regarding the preparation of magnetic polyurethane-based composite membranes that could be used to design some suitable devices with tailored properties, in order to improve the image quality in magnetic resonance imaging investigations and to suppress local image artifacts and blurring.

Tailoring Thermal and Electrical Properties of Jeffamine Segmented Polyetherimide Composite Films Containing BaTiO3 particles.

The continuous advancement of materials science has highlighted the ongoing need for additional studies on the main composite materials topics, particularly in the field of multifunctional nano-composites, towards improving their capability to meet multifaceted requirements in order to stimulate both scientific and technological development. In this study, we report the preparation and characterization of polyetherimides (PEIs) derived from 4,4'-(4,4'-isopropylidenediphenoxy) bis (phthalic anhydride) following a two-step polycondensation reaction using either 4,4'-(1,3-phenylenedioxy) dianiline, or Jeffamine ED-600 as comonomers, or a mixture of the two diamines. Based on the PEI containing flexible Jeffamine segments, polymer composite films were developed by incorporating BaTiO3 particles. The chemical structure and morphology of the composite films were investigated by FTIR spectroscopy and scanning electron microscopy. Thermal properties were determined by thermogravimetric analysis and differential scanning calorimetry. The influence of Jeffamine segments on the thermal decomposition process was investigated by TG/MS/FTIR measurements under air and nitrogen atmospheres. Based on the obtained data, the thermal decomposition mechanism was established and is discussed in accordance with the chemical structures of the polymers. The surface properties of the PEI and PEI-composite films were characterized by performing contact angle measurements. The addition of BaTiO3 increased the wettability of the surfaces. The dielectric characteristics of polymer composite films were investigated by broad band dielectric spectroscopy measurements. It was noticed that the addition of BaTiO3 nanoparticles to the copolymer matrix gradually enhanced the dielectric constant of the composites.

Composite Materials Based on Gelatin and Iron Oxide Nanoparticles for MRI Accuracy.

The majority of recent studies have focused on obtaining MRI materials for internal use. However, this study focuses on a straightforward method for preparing gelatin-based materials with iron oxide nanoparticles (G-Fe2O3 and G-Fe3O4) for external use. The newly obtained materials must be precisely tuned to match the requirements and usage situation because they will be in close touch with human/animal skin. The biocompatible structures formed by gelatin, tannic acid, and iron oxide nanoparticles were investigated by using FTIR spectroscopy, SEM-EDAX analysis, and contact angle methods. The physico-chemical properties were obtained by using mechanical investigations, dynamic vapor sorption analysis, and bulk magnetic determination. The size and shape of iron oxide nanoparticles dictates the magnetic behavior of the gelatin-based samples. The magnetization curves revealed a typical S-shaped superparamagnetic behavior which is evidence of improved MRI image accuracy. In addition, the MTT assay was used to demonstrate the non-toxicity of the samples, and the antibacterial test confirmed satisfactory findings for all G-based materials.

Composite Materials Based on Iron Oxide Nanoparticles and Polyurethane for Improving the Quality of MRI.

Polyether urethane (PU)-based magnetic composite materials, containing different types and concentrations of iron oxide nanostructures (Fe2O3 and Fe3O4), were prepared and investigated as a novel composite platform that could be explored in different applications, especially for the improvement of the image quality of MRI investigations. Firstly, the PU structure was synthetized by means of a polyaddition reaction and then hematite (Fe2O3) and magnetite (Fe3O4) nanoparticles were added to the PU matrices to prepare magnetic nanocomposites. The type and amount of iron oxide nanoparticles influenced its structural, morphological, mechanical, dielectric, and magnetic properties. Thus, the morphology and wettability of the PU nanocomposites surfaces presented different behaviours depending on the amount of the iron oxide nanoparticles embedded in the matrices. Mechanical, dielectric, and magnetic properties were enhanced in the composites' samples when compared with pristine PU matrix. In addition, the investigation of in vitro cytocompatibility of prepared PU nanocomposites showed that these samples are good candidates for biomedical applications, with cell viability levels in the range of 80-90%. Considering all the investigations, we can conclude that the addition of magnetic particles introduced additional properties to the composite, which could significantly expand the functionality of the materials developed in this work.

Matching the Cellulose/Silica Films Surface Properties for Design of Biomaterials That Modulate Extracellular Matrix.

The surface properties of composite films are important to know for many applications from the industrial domain to the medical domain. The physical and chemical characteristics of film/membrane surfaces are totally different from those of the bulk due to the surface segregation of the low surface energy components. Thus, the surfaces of cellulose acetate/silica composite films are analyzed in order to obtain information on the morphology, topography and wettability through atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and contact angle investigations. The studied composite films present different surface properties depending on the tetraethyl orthosilicate (TEOS) content from the casting solutions. Up to a content of 1.5 wt.% TEOS, the surface roughness and hydrophobicity increase, after which there is a decrease in these parameters. This behavior suggests that up to a critical amount of TEOS, the results are influenced by the morphology and topographical features, after which a major role seems to be played by surface chemistry-increasing the oxygenation surfaces. The morphological and chemical details and also the hydrophobicity/hydrophilicity characteristics are discussed in the attempt to design biological surfaces with optimal wettability properties and possibility of application in tissue engineering.

Preparation and Characterization of Electrospun Collagen Based Composites for Biomedical Applications.

Electrospinning is a widely used technology for obtaining nanofibers from synthetic and natural polymers. In this study, electrospun mats from collagen (C), polyethylene terephthalate (PET) and a blend of the two (C-PET) were prepared and stabilized through a cross-linking process. The aim of this research was to prepare and characterize the nanofiber structure by Fourier-transform infrared with attenuated total reflectance spectroscopy (FTIR-ATR) in close correlation with dynamic vapor sorption (DVS). The studies indicated that C-PET nanofibrous mats shows improved mechanical properties compared to collagen samples. A correlation between morphological, structural and cytotoxic proprieties of the studied samples were emphasized and the results suggest that the prepared nanofiber mats could be a promising candidate for tissue-engineering applications, especially dermal applications.

Preparation and Evaluation of Nanofibrous Hydroxypropyl Cellulose and ß-Cyclodextrin Polyurethane Composite Mats.

A series of nanofibrous composite mats based on polyurethane urea siloxane (PUUS), hydroxypropyl cellulose (HPC) and ß-cyclodextrin (ß-CD) was prepared using electrospinning technique. PUUS was synthesized by two steps solution polymerization procedure from polytetramethylene ether glycol (PTMEG), dimethylol propionic acid (DMPA), 4,4'-diphenylmethane diisocyanate (MDI) and 1,3-bis-(3-aminopropyl) tetramethyldisiloxane (BATD) as chain extender. Then, the composites were prepared by blending PUUS with HPC or ßCD in a ratio of 9:1 (w/w), in 15% dimethylformamide (DMF). The PUUS and PUUS based composite solutions were used for preparation of nanofibrous mats. In order to identify the potential applications, different techniques were used to evaluate the chemical structure (Fourier transform infrared-attenuated total reflectance spectroscopy-FTIR-ATR), morphological structure (Scanning electron microscopy-SEM and Atomic force microscopy-AFM), surface properties (contact angle, dynamic vapors sorption-DVS), mechanical characteristics (tensile tests), thermal (differential scanning calorimetry-DSC) and some preliminary tests for biocompatibility and microbial adhesion.

Versatile poly(vinyl alcohol)/clay physical hydrogels with tailorable structure as potential candidates for wound healing applications.

Physical poly(vinyl alcohol) (PVA) hydrogels containing up to 3% Laponite RD (LRD) were obtained by freezing/thawing method. The structure and the morphology of PVA/LRD hydrogels were evaluated by ATR-FTIR and SEM measurements, respectively. The morphological analysis of the hydrogels revealed the formation of clay agglomerates and large size aggregates at LRD concentrations above 2.5%. The rheological and mechanical properties of the PVA hydrogels in presence/absence of clay and their structural regeneration capacity after a large deformation were also investigated. The effect of LRD incorporation on the swelling behavior of the PVA hydrogels was discussed. The water vapor sorption capacity of PVA hydrogels decreases by clay addition. The analysis of in-vitro rifampicin release data indicated that the presence of a small amount of LRD into hydrogel affects the drug release mechanism. The antimicrobial activity of PVA hydrogels in presence/absence of LRD loaded with rifampicin against Staphylococcus aureus, Escherichia coli and Candida albicans was studied.