Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the ...favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels’ mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.
•Polysaccharide aerogel microspheres are investigated as carriers of drugs for oral administration.•Aerogels were loaded with ketoprofen and benzoic acid, poorly water soluble model drugs.•Starch, ...with the lowest specific surface area, was more prone to adsorb drug molecules.•Release of ketoprofen from alginate and pectin aerogel particles was sensitive to pH of the medium.•Results point out the possibilities of polysaccharide aerogels of tuning drug loading and release.
Polysaccharide-based aerogels in the form of microspheres were investigated as carriers of poorly water soluble drugs for oral administration. These bio-based carriers may combine the biocompatibility of polysaccharides and the enhanced drug loading capacity of dry aerogels. Aerogel microspheres from starch, pectin and alginate were loaded with ketoprofen (anti-inflammatory drug) and benzoic acid (used in the management of urea cycle disorders) via supercritical CO2-assisted adsorption. Amount of drug loaded depended on the aerogel matrix structure and composition and reached values up to 1.0×10−3 and 1.7×10−3g/m2 for ketoprofen and benzoic acid in starch microspheres. After impregnation, drugs were in the amorphous state in the aerogel microspheres. Release behavior was evaluated in different pH media (pH 1.2 and 6.8). Controlled drug release from pectin and alginate aerogel microspheres fitted Gallagher–Corrigan release model (R2>0.99 in both cases), with different relative contribution of erosion and diffusion mechanisms depending on the matrix composition. Release from starch aerogel microspheres was driven by dissolution, fitting the first-order kinetics due to the rigid starch aerogel structure, and showed different release rate constant (k1) depending on the drug (0.075 and 0.160min−1 for ketoprofen and benzoic acid, respectively). Overall, the results point out the possibilities of tuning drug loading and release by carefully choosing the polysaccharide used to prepare the aerogels.
Drug carriers tailored to fit the physicochemical properties of anticancer agents and the therapeutic peculiarities of tumor management are envisioned for improving the effectiveness/toxicity ratio ...of the current treatments. Polymeric micelles are attracting much attention owing to their unique beneficial features: i) core-shell structure capable to host hydrophobic drugs, raising the apparent solubility in aqueous medium; ii) size adequate for a preferential accumulation (passive targeting) within the tumor, exhibiting enhanced permeability and retention (EPR effect), and iii) unimers that modulate the activity of efflux pumps involved in multidrug resistance (MDR). This review focuses on amphiphilic poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) block copolymers, namely the linear poloxamers (Pluronic® or Lutrol®) and the X-shaped poloxamines (Tetronic®), as components of polymeric micelles able to play these three roles. Specific facets of poloxamers have been highlighted some years ago, but recently their wide range of possibilities is beginning to be fully elucidated and understood. Poloxamines are new excipients in the cancer arena and the comparison of their performance with that of poloxamers may enable to identify aspects of their architecture relevant for the optimization of micellar carriers. Clinical trials in progress indicate that drug-loaded polymeric micelles are beneficial regarding efficiency, safety, and compliance of the treatment and quality of life of the patients. The fact that some copolymers are already approved for internal use and several chemotherapy agents will be off patent soon may help to bring the clinical use of poloxamer- or poloxamine-based micelles into a reality in the coming years.
A supercritical carbon dioxide (scCO2)-assisted foaming/mixing method (SFM) was implemented for preparing dexamethasone (DXMT)-loaded poly(ɛ-caprolactone)/silica nanoparticles (PCL/SNPs) composite ...materials suitable for bone regeneration. The composites were prepared from PCL and mesoporous SNPs (MCM-41/SBA-15) by means of scCO2-assisted SFM at several operational pressures, processing times and depressurization conditions. DXMT was loaded into SNPs (applying a scCO2 solvent impregnation/deposition method – SSID) and into PCL/SNPs composites (using the SFM method). The effects of the employed operational and compositional variables on the physicochemical and morphological features as well as in the in vitro release profiles of DXMT were analyzed in detail. This work demonstrates that the above-referred scCO2-based methods can be very useful for the preparation of DXMT-loaded PCL/SNPs composites with tunable physicochemical, thermomechanical, morphological and drug release properties and suitable for hard-tissue regeneration applications.
Glycidyl methacrylate (GMA) and acrylic acid (AAc) were separately grafted onto polypropylene (PP) monofilament sutures by means of pre-irradiation using a 60Co γ-source, with the purpose of loading ...vancomycin via (i) covalent immobilization through the glycidyl groups of GMA and (ii) ionic interaction with AAc moieties. The effect of absorbed radiation dose, monomer concentration, temperature and reaction time on the grafting degree was evaluated in detail. GMA grafting ranged from 25% to 800% while the grafting yield of AAc onto PP could be tuned between 9% and 454%, at doses from 5 to 50kGy and a dose rate 13.7kGy/h. Grafting of GMA or AAc decreased the decomposition temperature and made the sutures swellable to a certain extent. GMA grafting led to a continuous, smooth and thick coating, which was suitable for immobilization of up to 1.9μg vancomycin per gram. The immobilized vancomycin enabled a reduction in the Staphylococcus aureus CFU adhered to the suture surface. On the other hand, dried AAc-functionalized sutures exhibited a rough and cracked surface which was responsible for a minor increase in the coefficient of friction. PP-g-AAc sutures exhibited pH-dependent swelling and remarkably high capability to host vancomycin (up to 109.9mg/g), particularly those with an intermediate degree of grafting. Some AAc-functionalized sutures were shown able to inhibit bacterial growth after successive challenges with fresh lawns. Therefore, tuning the yield of grafting of GMA or AAc may enable the preparation of drug-suture combination products that retain or release, respectively, antimicrobial agents.
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•Simvastatin was efficiently encapsulated in PLGA-based microparticles by spray-drying.•PLGA microparticles released osteogenic simvastatin hydroxyacid (SVA).•SVA concentration and ...microparticle formulation affected MSC proliferation and differentiation.•PLGA microparticles were embedded in fibroin/alginate beads alleviating SVA burst.•Microparticle-embedded fibroin/alginate beads promoted MSC differentiation into osteoblasts.
In the present work, we propose silk fibroin/alginate (SF/Alg) beads embedding simvastatin-loaded biodegradable microparticles as a versatile platform capable of tuning SVA release and in so doing osteogenic effects. In a first part of the study, microparticles of poly(lactic-co-glycolic) acid incorporating simvastatin either as lactone (SVL) or as hydroxyacid form (SVA) were prepared by spray-drying. While SVA-loaded microparticles released the drug in three days, long-term release of SVA could be obtained from SVL-loaded microparticles. In this latter case, SVL was promptly transformed to the osteogenic active SVA during release. When tested on mesenchymal stem cells, a time- and dose-dependent effect of SVL-loaded microparticles on cell proliferation and alkaline phosphatase (ALP) activity was found. Thereafter, SVL-loaded microparticles were embedded in SF/Alg beads to limit the initial simvastatin burst and to achieve easier implantation as well. Microparticle-embedded beads showed no cytotoxicity while ALP activity increased. If correctly exploited, the developed system may be suitable as osteogenic polymer scaffolds releasing correct amount of the drug locally for long time-frames.
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Superamphiphobic surfaces were evaluated as a tool to prepare spherical particles from polymers and solvents of very diverse nature, under mild conditions and with 100% drug ...encapsulation yield. Different from bioinspired superhydrophobic surfaces suitable only for aqueous dispersions, the superamphiphobic platforms allowed the formation of spherical droplets when solvents of any polarity were deposited onto them. Spherical poly(d,l-lactide-co-glycolide) (PLGA) particles were synthesized by placing drops of PLGA/ciprofloxacin suspensions in dioxane on a superamphiphobic surface followed by solvent evaporation. The particles prepared covering a wide range of PLGA/ciprofloxacin weight ratios delivered a 20% dose in the first 24h and then sustained the release of the remaining drug for more than 1month. The particles, both freshly prepared and after being 26days in the release medium, showed efficiency against different types of microorganisms. The developed polymer- and solvent-independent approach could be useful for microencapsulation with very high efficiency of active substances of varied nature into size-tunable particles for a wide range of applications in an affordable and cost-effective manner.
Temperature-sensitive polymeric micelles were prepared from dextran grafted with poly( N -isopropylacrylamide) (PNIPAAm) or polyethylene glycol methyl ether (PEGMA) via controlled radical ...polymerization and evaluated as delivery systems of the anticancer drug methotrexate (MTX). Polymer-grafting was carried out after introduction of initiating groups onto the polysaccharide backbone, without the need for protection of hydroxyl groups and avoiding the use of toxic solvents. Temperature-responsive dextran-based copolymers were designed to exhibit self-aggregation behaviour, affinity for MTX and high cellular internalization. In addition, some grafted polymers incorporated 2-aminoethyl methacrylate to reinforce MTX encapsulation in the micelles by means of ionic interactions. Dextran-based micelles were cytocompatible and had an appropriate size to be used as drug carriers. MTX release was dependent on the pH and temperature. The combination of poly(2-aminoethylmethacrylate) and PNIPAAm with the dextran backbone permitted the complete release of MTX at normal physiological temperature. Co-polymer micelles were highly internalized by tumour cells (CHO-K1) and, when loaded with MTX, led to enhanced cytotoxicity compared to the free drug.
The aim was to study how factors such as temperature, alcoholic degree, and amino acids supplementation are able to influence the content of tyramine, histamine, 2-phenylethylamine, tryptamine and ...their precursor amino acids in winemaking process. Biogenic amines and amino acids were quantified at the beginning, middle and end of alcoholic fermentation, and at the end of malolactic fermentation. In general, samples produced with amino acid supplementation did not show the highest concentrations of biogenic amines, except for histamine, which content increased with the addition of the four amino acids. The synthesis of tyramine was mainly affected by the temperature and alcoholic degree, the formation of phenylethylamine was largely influenced by alcoholic degree, and tryptamine synthesis principally depended on temperature. Interestingly, there was interaction between these three factors for the biogenic amines studied. In conclusion, winemaking conditions should be established depending on the biogenic amine which synthesis is required to be controlled.
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•The effect of temperature, alcohol, and amino acid content on biogenic amines (BA) in red wine•Biogenic amines and amino acids were quantified throughout the winemaking process.•Amino acid supplementation only affected histamine content.•Tyramine, phenylethylamine, and tryptamine level mainly depended on A° and Tª.•Winemaking conditions should be established depending on BA synthesis.
The goal of this work was to synthesize hybrid thin films prepared combining polyamide-6 (N6) and microcellulose (CE) at various weight ratios. Products exhibited improved mechanical properties, ...temperature-tunable hydrophilicity, and antimicrobial features. The obtained N6@CE films were grafted with
N
-vinylcaprolactam (NVCL) using gamma-rays, providing temperature responsiveness in a range of 37–38 °C. The grafting degree was studied as a function of CE percentage on the film, monomer concentration, and absorbed dose. The grafting degree increased with the percentage of CE on the film, and the maximum grafting was achieved at monomer concentration and the irradiation dose of 20% NVCL and 20 kGy, respectively. NVCL grafting was confirmed by SEM,
13
C-CPMAS NMR, FTIR-ATR, and XPS. SEM images attested formation of nanopores on the structure, caused by the grafting process, that consequently triggering on the new characteristics of the final materials. Potential performance of the composites as wound dressings was investigated in terms of their capability to loading and release of antimicrobial agents, such as vancomycin and benzalkonium chloride. NVCL grafting enhanced the uptake of both drugs, especially benzalkonium chloride, and regulated their release demonstrating antimicrobial effectiveness against
Staphylococcus aureus
.
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