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.
Polysaccharide-based aerogels provide high added-value lightweight materials with outstanding surface area and open porosity, susceptible to be loaded with active compounds in pharmaceutical ...applications. Aerogels are obtained by coupling sol–gel processing to a suitable drying technology, usually supercritical drying. The size and morphology of aerogels can be customized by means of the choice of the proper processing technology. Display omitted
► State-of-the-art of polysaccharide aerogels for pharmaceutical uses are described. ► Aerogel technology provides highly porous, high surface area, lightweight carriers. ► Biodegradable and biocompatible carriers with high drug loading capacity are obtained. ► Processing parameters strongly influence the resulting end material properties. ► Case studies on polysaccharide aerogels and their use in drug delivery are described.
Polysaccharides are regarded as key ingredients for the production of bio-based materials in life sciences (e.g., food, cosmetics, medical devices, pharmaceutics). The biodegradability and biocompatibility of these biopolymers, coupled to the large variety of chemical functionalities they encompass, make them promising carriers for drug delivery systems. Aerogels are a special class of nanoporous materials with growing interest in biomedical and pharmaceutical applications due to their open pore structure and high surface area. Polysaccharide-based aerogels result in highly porous (ɛ=90–99%), lightweight (ρ=0.07–0.46g/cm3) drug carriers with high surface area (Sa=70–680m2/g), able to provide enhanced drug bioavailability and drug loading capacity. This review focuses on the state-of-the-art of the production of polysaccharide-based aerogels with emphasis on the influence of processing parameters on the resulting end material properties. Case studies on polysaccharide-based aerogels from several sources and own results as well as their behavior regarding drug loading capacity and release are described.
► Starch aerogel microspheres were prepared by thermal gelation from emulsions. ► No chemical crosslinkers were used to promote gelation. ► The process did not use any toxic organic solvent for ...applications in life science. ► Starch aerogel microspheres have high internal surface area and loading capacity. ► This material can be used as biocompatible+biodegradable carriers of chemicals.
The inherent biocompatibility and biodegradability of starch, a natural polysaccharide-based product, allows its use in the form of microspheres as a chemical carrier for life science applications. However, current methods of preparation of starch microspheres utilize chemical crosslinkers and drying methods (air drying, freeze drying) that leads to problems of degradability of the matrix and low specific surface areas and chemical loading capacities. In this work, corn starch aerogel microspheres, a special class of nanoporous materials, were prepared by the combination of an emulsion-gelation method and supercritical drying without the use of chemical crosslinkers. Effects of gelation temperature (368, 393 and 413K), oil-to-aqueous starch solution ratio (1:1, 2:1, 3:1) and surfactant content (3, 6 and 10% (w/w)) on the textural and morphological properties of the aerogel material were studied. The obtained starch aerogels were characterized using nitrogen adsorption–desorption measurements, helium pycnometry, CHN elemental analyses, thermogravimetry and scanning electron microscopy. Spherical starch aerogel microspheres with tailor-made specific surface areas (34–120m2g−1 range) and particle sizes (215–1226μm diameter range) were obtained. Aerogel textural properties were mainly influenced by the gelation temperature used, whereas the particle morphology depended on the three processing parameters studied. High specific chemical loading capacity (1.1×10−3gm−2) of the aerogel microspheres was obtained using ketoprofen as a model compound.
Stimulation of the dorsolateral periaqueductal grey matter (dlPAG) in rats evokes an active defensive behaviour together with a cardiorespiratory response characterised by tachypnoea, tachycardia and ...hypertension. The dlPAG neurons involved in these responses are excitatory, presumably glutamatergic, due to the presence of vesicular glutamate transporter VGLUT2 within their axon terminals. Previously, our group described a functional interaction between dlPAG and the pontine A5 region. Accordingly, in the present work, in order to characterize the role of glutamate within this interaction, experiments were carried out in spontaneously breathing anaesthetized rats (sodium pentobarbitone 60 mg/kg i.p., suplemented with 20 mg/kg i.p.). The cardiorespiratory response evoked by electrical stimulation of the dlPAG (1 ms pulses, 20–50 μA, given at 100 Hz, during 5 s) was analysed before and after the microinjection, within the A5 region, of either kynurenic acid (non-specific glutamate receptor antagonist; 5–10 nmol), DAP-5 (NMDA antagonist; 1 pmol), CNQX (non-NMDA antagonist; 1 pmol) or MCPG (metabotropic antagonist; 0,1 nmol). Kynurenic acid decreased the intensity of both the tachypnoea (
p
< 0,001) and tachycardia (
p
< 0,001) induced by dl-PAG stimulation. Blockade of no-NMDA receptors reduced the increase of respiratory frequency, heart rate and pressor response to dl-PAG stimulation (
p
< 0,01,
p
< 0,001,
p
< 0,05 respectively). Blockade of either NMDA or metabotropic receptors reduced the dlPAG-evoked tachycardia and pressor response (
p
< 0,01;
p
< 0,05 respectively). These results suggest a neuromodulatory role for A5 region via glutamate neurotransmission of the dlPAG-evoked cardiorespiratory response, confirming the role of the ventrolateral pons in the neuronal circuits involved in respiratory and heart rate control.
Supercritical extraction of the solvent from organic gels, like polysaccharides, enables the production of highly porous biodegradable aerogel with a high surface area. The structural properties of ...the produced aerogel depend mainly on the preparation methods and the composition of the gel phase. This work presents a new method to produce biodegradable microspherical alginate aerogels particles using an emulsion technique. Water in oil (W/O) emulsion was produced by mixing a Na–alginate solution (dispersed phase) with oil (continuous phase) followed by cross-linking the dispersed phase to form the gel particles. The gelation parameters as well as the emulsion process parameters were investigated in order to control the form and the structural properties of the produced alginate aerogel. Alginate aerogel microspherical particles with a high surface area up to 680
m
2/g and relatively large pore volume up to 4.0
cm
3/g and different mean particle diameters ranging from 25
μm to few hundred microns were produced using the presented method.
Cardiovascular disease (CVD) is the leading cause of death. The mainly risks factors for CVD are diabetes, hypertension and high levels of homocysteine (Hcys), among others. Paraoxonase 1 (PON1) has ...been proposed as an antiatherogenic target for its ability to hydrolyzing oxi-Low-Density-Lipoproteins (LDL) and Hcys-thiolactone. Thus, the aim of the present study was to evaluate the association of Hcys levels, and the activities and concentration of PON1, as well as vitamin B from the diet with a risk for CVD.
A case-control study was carry out in patients with cardiovascular diseases (CVD), Arterial hypertension, but not CVD (AH), and in healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, intake of vitamin B, Hcys, serum amyloid A (SAA), PON1 concentration, and PON1 activities (Arylesterase activity (ARE), Lactonase activity (LAC), and CMPA activity (CMPA)) were evaluated.
The CVD group had the highest concentration of Hcys and SAA than in the AH and control groups (p < 0.01). ARE, LAC, and CMPA activities and PON1 concentration were lowest in the CVD group. A positive-independent association between Hcys levels and CVD was found (OR = 2.09; 95% CI: 1.69–2.56) and this increase when it was adjusted by age, BMI, ApoA1, vitamin B intake, SAA, and PON1 (OR = 14.41; 95% CI: 1.75–118.71). LAC and CMPA, as well as PON1 concentration, were inversely associated with CVD.
LAC activity, PON1 concentration, and Hcys levels might be good biomarkers for CVD and their association could be modified by the intake of vitamin B.
•Patients with cardiovascular disease (CVD) had higher Hcys and SAA levels than controls.•Activities and concentration of PON1 were low in patients with CVD.•Hcys levels were associated with an increase in the OR of belonging to the CVD group.•LAC activity, PON1 concentration, and Hcys levels might be good biomarkers for CVD.
•Starch aerogel microspheres were assessed as delivery carriers for active compounds.•Starch source and concentration and stirring rate changed final aerogel properties.•Aerogel micronization led to ...faster solvent extraction by supercritical drying.•Long supercritical drying times were detrimental to the textural properties.•Ketoprofen release from starch aerogels correlated well with Korsmeyer–Peppas model.
Supercritical and compressed fluid technology provides a powerful tool for particle design and engineering. On the other hand, aerogels are nanoporous materials holding many world-class properties. However, the morphology of the end product can be the limiting factor for aerogels in some applications. The integration of different technologies for the production of particles can lead to a breakthrough in aerogel production. In this work, the combination of the emulsion–gelation process with supercritical fluid extraction was tested as a versatile technology for the production of microspherical aerogel particles. Novel natural product-based nanoporous materials (aerogels) based on starch were obtained using this method and were specifically targeted to chemical carriers for life science applications (e.g. pharmaceutics, tissue engineering, cosmetics, food, biotechnology, and agriculture). Aerogels in the form of cylinders and microspheres (400–800μm) with the intrinsic outstanding textural aerogel properties (high surface area – Sa=100–240m2/g, low density – ρ=0.10–0.25g/cm3, large porosity – ɛ=85–90%) were produced. The effect of micronization on the kinetics of the supercritical drying of the wet gel (in ethanol) was also studied. Thus the obtained aerogels were then tested for their use as active agent carriers regarding loading capacity using ketoprofen as model compound as well as the release behavior of the loaded active compound in aqueous media simulating physiological pHs.
•Patients with CVD had lower activity of PON1 Lactonase (LACase) than control patients.•LACase activity might be a new potential biomarker in CVD.•LACase activity is not influenced by the genetic ...polymorphisms of PON1.
Paraoxonase 1 (PON1) is important in the development of atherosclerosis, and it has become the subject of intensive research. Our aim was to evaluate the association of serum PON1 activity and polymorphisms with cardiovascular disease (CVD) using four different substrates.
Activity of PON1-related to arylesterase (AREase and 4-CMPAse), paraoxonase (PONase), and lactonase (LACase), and polymorphisms (A-162G, T-108C, L55M, and Q192R) were evaluated in subjects with CVD, cardiovascular risk factor (CFR), and controls. An ordered logistic-regression analysis of PON1 phenotypes was performed in the CVD group with respect to the control group.
Logistic-regression analysis showed that CC-108 genotype was associated with CRF and CVD. The CVD group had the lowest activities of PON1. The LACase might be a better biomarker for CVD (OR, 0.52; 95% CI, 0.44–0.61) followed by CMPAse (OR, 0.82; 95% CI, 0.77–0.86), AREase (OR, 0.98; 95% CI, 0.97–0.99) and PONase (OR, 0.99, 95% CI, 0.99–0.99). Logistic regression of PON1 phenotypes by haplotypes showed that LACase activity was not influenced by the polymorphisms and that it could be a new potential biomarker in the development of CVD. Larger scale longitudinal studies are required.
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