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A global release model is proposed to study the drug release from porous materials for pharmaceutical applications. This model is defined by implementing a compartmental model where the release profile could be explained as the combination of mass transfer phenomena through three compartments as well as a desorption process or dissolution process from the support. This model was validated with five different systems produced with supercritical CO

Marigold oil is a product of great industrial interest thanks to its wide range of medicinal and wound-healing properties. In this work, supercritical carbon dioxide was used to recover marigold essential oil from the hexane solvent extract of marigold flowers, the floral “concrete”. This starting material was mixed with synthetic paraffinic waxes to heighten its melting point and viscosity, thus, improving material processability. Supercritical fluid extraction and fractionation of the modified marigold “concrete” was carried out, and the effect of pressure and CO2 mass flow rate was studied. The pressure was varied from 80 to 180 bar, keeping the temperature constant at 40 °C: the higher the pressure, the larger the CO2 solvent power and extraction yield (up to 9.40% w/w). Nevertheless, the optimum between productivity and process selectivity was found at 100 bar. By changing the CO2 mass flow rate (from 1.20 to 1.50 kg/h), we noted that mass transfer resistance was located externally. GC-MS analysis showed that the most abundant compounds in the oil were δ-cadinene (25%), γ-cadinene (16%), τ-muurolol (6.5%), and α-muurolene (6%). Moreover, the traces of oil and waxes showed no mutual contamination between lighter species and waxes, meaning that the fractionation step was successful.

Liposomes have been used for several decades for the encapsulation of drugs and bioactives in cosmetics and cosmeceuticals. On the other hand, the use of these phospholipid vesicles in food applications is more recent and is increasing significantly in the last ten years. Although in different stages of technological maturity—in the case of cosmetics, many products are on the market—processes to obtain liposomes suitable for the encapsulation and delivery of bioactives are highly expensive, especially those aiming at scaling up. Among the bioactives proposed for cosmetics and food applications, vitamins are the most frequently used. Despite the differences between the administration routes (oral for food and mainly dermal for cosmetics), some challenges are very similar (e.g., stability, bioactive load, average size, increase in drug bioaccessibility and bioavailability). In the present work, a systematic review of the technological advancements in the nanoencapsulation of vitamins using liposomes and related processes was performed; challenges and future perspectives were also discussed in order to underline the advantages of these drug-loaded biocompatible nanocarriers for cosmetics and food applications.

Traditional and supercritical CO

In this study, SuperLip, an innovative technology assisted by supercritical carbon dioxide (SC–CO2), was used to produce unloaded and vitamin D3 (VD3)-loaded nanoliposomes. Vesicles were produced using hydrogenated and nonhydrogenated phosphatidylcholine from food-grade lecithins at ratios of 30:70, 20:80 and 0:100. SuperLip was operated at 100 bar and 40 °C using water flow rates ranging from 2.5 to 10 mL/min. The results showed that unloaded liposomes produced by SuperLip presented a unimodal size distribution at a water flow rate of 10 mL/min, regardless of the phospholipid ratio, and mean diameters ranging from 125 to 141 nm. VD3-loaded liposomes also presented a unimodal size distribution at this water flow rate, but slightly higher diameters that ranged from 144 to 252 nm. Furthermore, the addition of 20% purified phospholipids to liposomes led to an increase in the mean size of VD3-loaded vesicles from 144 to 218 nm and an increase in the encapsulation efficiency from 66.7 to 88.9%.

Background Curcumin and vitamin D3 (VD3) are nutraceutical compounds that exert important roles in the human health. Nanoencapsulation in liposomes appears as a suitable target delivery system that can also enhance the bioavailability of these biomolecules. Methods Vesicles were prepared using different ratios of hydrogenated and non-hydrogenated phospholipids, obtained from soy and egg-yolk. A supercritical CO2 assisted process was used to produce the nanoliposomes. The operative parameters were 40 °C and 100 bar, using a water flow rate of 10 mL/min. Nanoliposomes were characterized by scanning electron microscopy and dynamic light scattering to determine their morphology and stability; whereas biomolecules encapsulation efficiency and release kinetics were measured by a UV/Vis spectrophotometer. Antioxidant activity and the effect of stress-induced conditions on the nanoliposomes were also investigated. Significant findings Nanoliposomes mean diameters ranged from 128 to 228 nm, with encapsulation efficiencies up to 95% for curcumin and 74% for VD3. The addition of 30% w/w of saturated phospholipids to the starting formulation promoted an increase in size of vesicles and a consequent increase in the encapsulation efficiency of both biomolecules. The antioxidant activity of curcumin was preserved after processing and the co-loaded nanovesicles demonstrated a good stability under different stress conditions.

With the aim of increasing the mechanical and biological properties of different materials, a supercritical CO2 (SC-CO2) assisted technique was used to include a polymer with a natural origin (levan) in membranes of cellulose acetate (CA) and polyvinylidenefluoride-co-hexafluoropropylene (PVDF-HFP). CA-levan membranes were characterized by interconnected pores ranging from 9 to 13 μm; due to levan addition, composite membranes increased their mechanical resistance and cells adhesion (from 8% to 30%). In the second system, the processing of a PVDF-HFP-DMSO-levan colloidal suspension system caused a morphological modification and the generation of a foam-like structure; a decrease of the mechanical resistance and an increase of cells adhesion (from 8% to 35%) were observed. Stress-strain responses for both systems were fitted using two different hyperelastic equations, Yeoh and Ogden; deviations from experimental data lower than 15% were obtained. In conclusion, SC-CO2 assisted process was able to generate composite structures with levan, accessible to the cells; i.e., transforming polymers like CA and PVDF-HFP in potentially useful materials for biological applications.

Agarose-based gels were produced either by freeze-drying or by supercritical drying for crystal violet (CV) removal from aqueous solutions. The microporosity features of these structures highly affected the final adsorption properties. In particular, agarose cryogels were characterized by a macroporous and irregular morphology, with a low value of specific surface area (11 ± 6 m2/g) with respect to the nanoporous agarose aerogels (154 ± 12 m2/g). To test the efficacy of CV removal, two different types of adsorption test were performed, i.e., batch-mode and multi-step mode. Operating in the multi-step mode, the adsorption performance was larger both for cryogels and aerogels, since this adsorption method allowed a more effective contact between CV and agarose adsorbent. In particular, using 300 mg of cryogels, a removal efficiency of 74% was achieved; using the same quantity of aerogels, 96% of removal efficiency was reached after eight steps of adsorption. Desorption of CV from aerogels was realized using ascorbic acid and, after regeneration, 93% of removal efficiency was preserved, even after three cycles in multi-step filtration mode.

TiO2-loaded poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-coHFP) membranes were produced by supercritical CO2-assisted phase inversion. Three different TiO2 loadings were tested: 10, 20, and 30 wt% with respect to the polymer. Increasing the TiO2 amount from 10 wt% to 20 wt% in the starting solution, the transition from leafy-like to leafy-cellular morphology was observed in the section of the membrane. When 30 wt% TiO2 was used, the entire membrane section showed agglomerates of TiO2 nanoparticles. These polymeric membranes were tested to remove Sudan Blue II (SB) dye from aqueous solutions. The adsorption/photocatalytic processes revealed that membrane morphology and TiO2 cluster size were the parameters that mainly affected the dye removal efficiency. Moreover, after five cycles of exposure of these membranes to UV light, SB removal was higher than 85%.

In this work, the effect of two processes, i.e., freeze-drying and supercritical CO2 (SC-CO2) drying, on the final morphology of agarose-based porous structures, was investigated. The agarose concentration in water was varied from 1 wt% up to 8 wt%. Agarose cryogels were prepared by freeze-drying using two cooling rates: 2.5 °C/min and 0.1 °C/min. A more uniform macroporous structure and a decrease in average pore size were achieved when a fast cooling rate was adopted. When a slower cooling rate was performed instead, cryogels were characterized by a macroporous and heterogenous structure at all of the values of the biopolymer concentration investigated. SC-CO2 drying led to the production of aerogels characterized by a mesoporous structure, with a specific surface area up to 170 m2/g. Moreover, agarose-based aerogels were solvent-free, and no thermal changes were detected in the samples after processing.

This work proposes an improvement of the traditional electrospraying process, in which supercritical carbon dioxide (SC-CO2) is used to produce poly(lactic-co-glycolic acid) (PLGA) nanoparticles. The experiments were performed at different PLGA concentrations (1, 3 and 5% w/w), applied voltages (10 and 30 kV) and operating pressures (80, 120 and 140 bar). It was found that working at 140 bar and 30 kV, spherical nanoparticles, with mean diameters of 101 ± 13 nm and 151 ± 45 nm, were obtained, when solutions at 1% w/w and 3% w/w PLGA were electrosprayed, respectively. Increasing PLGA concentration up to 5% w/w, a mixture of fibers and particles was observed, indicating the transition to the electrospinning regime.

In this short review, drug delivery systems, formed by polysaccharide-based (i.e., agarose, alginate, and chitosan) aerogels, are analyzed. In particular, the main papers, published in the period 2011–2020 in this research field, have been investigated and critically discussed, in order to highlight strengths and weaknesses of the traditional production techniques (e.g., freeze-drying and air evaporation) of bio-aerogels with respect to supercritical CO2 assisted drying. Supercritical CO2 assisted drying demonstrated to be a promising technique to produce nanostructured bio-aerogels that maintain the starting gel volume and shape, when the solvent removal occurs at negligible surface tension. This characteristic, coupled with the possibility of removing also cross-linking agent residues from the aerogels, makes these advanced devices safe and suitable as carriers for controlled drug delivery applications.

Traditional and supercritical CO2 assisted processes are frequently used to produce microparticles formed by a biopolymer containing an active principle to improve the bioavailability of the active principle. However, information about the internal organization of these microparticles is still scarce. In this work, a suspension of dextran + Fe3O4 nanoparticles (model system) and a solution of polyvinylpyrrolidone (PVP) + curcumin were used to produce spherical microparticles by supercritical CO2 processing. Periodic dynamic light scattering measurements were used to analyze the evolution of the microparticles dissolution, size, and size distribution of the guest active principle in the polymeric matrix. It was found that curcumin was dispersed in the form of nanoparticles in the PVP microparticles, whose size largely depended on its relative concentration. These results were validated by transmission electron microscopy and scanning electron microscopy of the PVP microparticles and curcumin nanoparticles, before and after the dissolution tests.

Cuticular waxes can be used in high-value applications, including cosmetics, foods and nutraceuticals, among the others. The extraction process determines their quality and purity that are of particular interest when biocompatibility, biodegradability, flavor and fragrance are the main features required for the final formulations. This study demonstrated that supercritical fluid extraction coupled with fractional separation can represent a suitable alternative to isolate cuticular waxes from vegetable matter that preserve their natural properties and composition, without contamination of organic solvent residues. Operating in this way, cuticular waxes can be considered as a fingerprint of the vegetable matter, where C27, C29 and C31 are the most abundant compounds that characterize the material; the differences are mainly due to their relative proportions and the presence of hydrocarbon compounds possessing other functional groups, such as alcohols, aldehydes or acids. Therefore, selectivity of supercritical fluid extraction towards non-polar or slightly polar compounds opens the way for a possible industrial approach to produce extracts that do not require further purification steps.

The production of polymeric micro- and nanoparticles with regular morphology and controlled size and distribution is a relevant target for many fields, from pharmaceutical to nutraceutical, from energetics to fine chemical. In this work, an improved micronization process is proposed, called supercritical assisted electrospray, for the production of biocompatible polyvynilpyrrolidone (PVP) particles loaded with quercetin. This supercritical process can largely improve the traditional electrospray performance, thanks to the addition of supercritical CO2 in the liquid polymeric solution at the beginning of the process. Operating in this manner, an expanded liquid is formed, characterized by a reduced viscosity and surface tension. Repeatable PVP microparticle diameters and distributions were obtained, ranging between 0.47 ± 0.24 µm and 6.01 ± 3.60 µm at PVP concentrations from 1% to 7% w/w, and between 1.71 μm ± 1.07 μm and 2.08 μm ± 1.18 μm, for 1% and 3% w/w PVP particles loaded at 7% w/w quercetin, respectively, working at 120 bar, 35 ℃ and 30 kV.

BACKGROUND: Artemisia annua L. extraction is traditionally performed using hexane; the process is simple, but not selective. In this work, a strategy to concentrate artemisinin and the other similar active principles in the final extract is proposed, combining cheapness of maceration and selectivity of SC‐CO₂ processing. RESULTS: Hexane extraction produced a solid, waxy extract with a yield of 3.3% w/w with respect to the starting vegetable material. Then, SC‐CO₂ processing of this solid extract was performed operating at 0.8 kg h⁻¹ SC‐CO₂ flow rate and at different operative parameters. Very selective conditions were found operating at 90 bar and 50°C, obtaining a final product containing more than 71% w/w of active compounds (artemisinin, artemisin and dehydroartemisinin). CONCLUSION: Using this approach, a product more than 2.6 times richer in artemisinin than the one obtained by conventional techniques and about 2 times richer than direct CO₂ extraction, was obtained. Another relevant result is that the overall process scheme is cheaper than direct CO₂ extraction, since a high pressure extractor about 20 times smaller can be used, to process the waxy product obtained by hexane extraction. © 2018 Society of Chemical Industry

The recovery of active ingredients from vegetable matter is one of the most attractive research fields in the literature. The perspective that moves this large interest, is the possibility to selectively solubilize the compounds of interest in SC-CO2 and to avoid the use of organic solvents that pollute the environment, the products and the processed material. Nevertheless, care must be devoted in selecting process arrangement and extraction conditions, minimizing co-extracted compounds. Fractional extraction and/or fractional separation should be a possible solution. The addition of a co-solvent has been proposed in the case of less soluble compounds in pure SC-CO2; but, the so-called supercritical antisolvent extraction could represent a valuable solution for these compounds.

In this work, the comparison between PVDF-HFP porous structures loaded with 3% w/w curcumin (Cm), produced by supercritical assisted processes, was performed. In the case of membranes, different operative conditions (from 250 bar/35 °C to 150 bar/55 °C) and polymer concentrations (from 10 to 30% w/w) were tested. A cellular membranes morphology was observed and porosity values up to 89% were measured. Cm release was prolonged from 20 h to 26 h changing the PVDF-HFP membrane concentration from 20 to 30% w/w. PVDF-HFP-Cm aerogels were produced by supercritical drying, operating at 200 bar and 45 °C. A nanofibrous aerogels morphology was obtained with open and interconnected pores, reaching porosity values of 94%. The maximum Cm release was prolonged up to 44 h for 12% w/w PVDF-HFP aerogel. Kosmeyers-Peppas model produced a fair good representation of the Cm release experimental results for PVDF-HFP-Cm membranes and aerogels.

In this work, the effect of two processes, i.e., freeze-drying and supercritical CO2 (SC-CO2) drying, on the final morphology of agarose-based porous structures, was investigated. The agarose concentration in water was varied from 1 wt% up to 8 wt%. Agarose cryogels were prepared by freeze-drying using two cooling rates: 2.5 °C/min and 0.1 °C/min. A more uniform macroporous structure and a decrease in average pore size were achieved when a fast cooling rate was adopted. When a slower cooling rate was performed instead, cryogels were characterized by a macroporous and heterogenous structure at all of the values of the biopolymer concentration investigated. SC-CO2 drying led to the production of aerogels characterized by a mesoporous structure, with a specific surface area up to 170 m2/g. Moreover, agarose-based aerogels were solvent-free, and no thermal changes were detected in the samples after processing.

Co-crystallization of amorphous poly(2,6-dimethyl-1,4-phenylene) oxide (PPO) films, as induced by sorption at different temperatures of many liquid guest molecules, is explored. Both for co-crystalline (CC) and corresponding nanoporous-crystalline (NC) films, kinds of and degree of planar orientation, which are relevant for their properties and applications, can be controlled by the guest sorption procedure. In particular, crystalline polymer chain orientation preferentially perpendicular to the film plane is favored by bulky guest molecules and by low guest sorption temperatures, i.e. by slow guest uptakes. Guest sorption kinetics and Scanning Electron Microscopy ( SEM ) support a simple mechanism that rationalizes the kinds of planar orientation of crystalline PPO chains. Slow guest uptakes imply polymer co-crystallization in spatial confinement, producing lamellae that are oriented flat-on to the film surface and hence polymer chain axes preferentially perpendicular to the film plane (c⊥ orientation). Fast guest uptakes imply polymer co-crystallization leading to fibrils that are parallel to the film surface and hence to polymer chain axes being preferentially parallel to the film plane (c// orientation).

The use of a supercritical CO2 assisted drying process for the preparation of RuO2 nanoparticles loaded PVDF HFP aerogels is reported in this work. Morphological, mechanical, and electrochemical analyses were performed on the obtained nanocomposites, to ascertain their performance as supercapacitor devices. The supercritical process allowed a homogeneous distribution of the additive in the polymeric matrix and avoided gel shrinkage. Cycling voltammetry and charge/discharge measurements demonstrated an excellent behavior for the nanocomposites. The supercapacitor, at 60% w/w RuO2, exhibited a specific capacitance of 149.3 F/g at a scan rate of 10 mVs−1, and a Coulombic efficiency of 98%. Through the integration of the discharge curves, the specific capacitances were also calculated. In particular, doubling the current density, e.g., from 1.0 A/g to 2.0 A/g, the specific capacitance only reduced of about 20%.

The production of biocompatible nanocarriers, to induce a controlled, sustained and/or targeted drug delivery, is a fascinating nanotechnology challenge. Among the possible nanocarriers, niosomes are non-ionic compounds, with a lipophilic tail and a hydrophilic head, that can self-assemble in aqueous dispersions and can show a good stability over time. In this work, a continuous process, assisted by supercritical CO2, was used for the production of empty and theophylline loaded niosomes. The optimal results, in terms of niosomes nanometric dimension and stability verified up to 30 days, were obtained processing an ethanolic solution at a 90/10 Span® 80 to Tween® 80 ratio. A drug encapsulation efficiency of 85 % was measured when the supercritical process was carried out using a water flow rate of 1 mL/min. Theophylline release time was prolonged up to 5-folds, when this active compound was loaded in niosomes prepared at the largest surfactant to water ratio (100 mg/g).

Supercritical fractional extraction and separation scheme, was used to process Artemisia annua L., producing extracts enriched in active antimalarial principles. The best results were obtained when extraction was performed at 100 bar, 40 °C and the first separator was operated at the same pressure and at −7 °C. Paraffinic co-extracted compounds were selectively recovered in the first separator, confirming the efficiency of the fractional cooling separation and a concentration of 35% w/w of active compounds was obtained in the second separator. Artemisinin was the major active compound in the extract; but, other two active compounds, artemisin and dehydroartemisinin, were also largely found. Other co-extracted compounds belonged to Artemisia essential oil. Different SC-CO2 flow rates were tested: an increase from 0.8 to 1.2 kg/h did not determine appreciable variations of the extraction rate of the various compounds, indicating that internal mass transfer resistance mainly controlled the extraction process.

This work proposes a modeling of the mechanical properties of porous polymers processed by scCO₂, using a phenomenological approach. Tensile and compression tests of alginate/gelatin and cellulose acetate/graphene oxide were modeled using three hyperelastic equations, derived from strain energy functions. The proposed hyperelastic equations provide a fair good fit for mechanical behavior of the nanofibrous system alginate/gelatin (deviations lower than 10%); whereas, due to the presence of the solid in the polymer network, a four-parameter model must be used to fit the composite cellulose acetate/graphene oxide behavior. Larger deviations from the experimental data were observed for the system cellulose acetate/graphene oxide because of its microporous structure. A finite element method was, then, proposed to model both systems; it allowed a realistic description of observable displacements and effective stresses. The results indicate that materials processed using scCO₂, when submitted to large stresses, do not obey Hooke´s law and must be considered as hyperelastic.

In this work, supercritical phase inversion was used to produce membranes of cellulose acetate, loaded with a highly hydrophobic drug, quercetin, with antifungal properties. Changing process parameters, such as polymer concentration (5%, 10% and 15% w/w), pressure (100 and 200 bar) and temperature (45 and 50 °C), different membrane morphologies and pores size were obtained. Operating in this way, it was possible to control quercetin release: the existence of macrovoids (i.e., finger-like structure) promoted a faster drug release (about 200 min); whereas, cellular structures favored a prolonged drug release (up to 1400 min). These membranes were tested against two types of fungi (Kluyveromyces lactis and Yarrowia lipolitica), obtaining an efficient and prolonged antifungal effect, overcoming the problems of quercetin hydrophobicity.

In this work is proposed a critical review of the scientific literature about the extraction of products of industrial interest from Cannabis sativa L., like cannabinoids, essential oil and seed oil, using supercritical and subcritical CO2. Traditional techniques are also reviewed and critically discussed to evidence the advantages of CO2 processing. The extracts can be also used in pharmaceutical and biomedical formulations, in form of co-precipitates and capsules, to improve active compounds bioavailability and performance. Further studies can be required, mainly based on the analysis of mass transfer resistances during extraction and on solubility data of the compounds to be extracted, to improve process selectivity and the purity of the extracts obtained.

Ampicillin loaded liposomes were entrapped in alginate aerogels to create a meta-carrier (a carrier within another carrier), to obtain a prolonged drug release. Liposomes with a diameter of 200 ± 77 nm and with an encapsulation efficiency of 69.5 ± 1.2% were produced using a supercritical assisted formation process (SuperLip). Then, they were entrapped into alginate gels, and the final loaded aerogels were obtained by supercritical CO2 drying. The successful entrapment of liposomes into aerogels was confirmed by EDX analysis. Drug release tests demonstrated that ampicillin release time from these meta-carriers was about 4 days; i.e., about twice than its release time from liposomes alone. Two mass transfer resistances in series operated in the overall drug release: one related to liposomes lipidic layers and one due to the presence of the alginate aerogel matrix.

Superabsorbent polymers (SAPs) are organic materials possessing high capacity to absorb and retain large volumes of water, saline and physiological solutions (at least 10–20 times their weight). The most commonly used SAPs are acrylated-based polymers that are not biodegradable or recyclable. To overcome these limits, carboxymethylcellulose (CMC) with hydroxyethylcellulose (HEC) hydrogels were synthetized in this work and dried using a supercritical assisted process at 200 bar and 45 °C. The solvent exchange procedure influenced the final aerogel morphology and, thus, the aerogel swelling ratio (SR). A solvent exchange starting from 50 % v/v ethanol, preserved the native gel nanofibrous morphology, producing a SR up to 20 times larger than the ones reported in the literature using the same process, corresponding to a water uptake larger than 500 times the weight of the dried aerogel.

Supercritical phase inversion was used to prepare new polymeric membranes, based on cellulose acetate and Laponite®, for tissue engineering applications. These composite membranes were characterized by a porous structure (porosity around 85%) with an average pore size ranging from about 9 to 13 μm depending on the initial weight ratio cellulose acetate/Laponite. This ratio also controlled thermal and mechanical properties of these membranes: Laponite modified membrane decomposition step and increased the membrane elasticity modulus up to 4 MPa while decreasing the percentage elongation at break from 240% to 180%. Laponite also increased material cells adhesion: thanks to its homogeneous inclusion into the membranes, a remarkable cells adhesion of around 80%, six times higher than the original material, was obtained.

Safety, easiness, and ecologically friendly preparation methods are key features in the fabrication of a portable supercapacitor. In this work, it is reported the use of supercritical CO2 (SC–CO2)-assisted gel drying for the direct preparation in a one-step of a novel porous and portable supercapacitor device. It consists of three layers, grown together and able to uptake a large amount of an ionic liquid, of an aerogel of Poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP): the middle layer is formed by PVDF-HFP alone and the top, and bottom layers are formed by PVDF-HFP aerogels containing dispersed molybdenum disulfide (MoS2) nanosheets (i.e., PVDF-HFP + MoS2). The produced supercapacitor device (PVMS) is characterized by a mesoporous structure with high surface area, taking advantage from both non-flammability and electrochemical stability of PVDF-HFP and high capacitance of MoS2 due to its fast ionic conductivity. The supercapacitor, at the optimized operative conditions, achieves an excellent specific capacitance of 176 F/g and a very high energy density of 97.8 Wh/Kg at a power density of 0.65 of kW/kg (current density 0.6 A/g), that still remains 76.4 Wh/kg at 5.1 kW/kg (current density 5 A/g, specific capacitance of 138.2 F/g). The device shows good stability in an ionic liquid electrolyte, suggesting that the proposed process can be a new opportunity to produce highly bulky improved supercapacitors.

Chitosan (CH) is one of the polymers most frequently proposed in form of hydrogels for tissue engineering (TE) applications. It is often crosslinked with the aim of improving its stability and mechanical properties. In this work, a supercritical carbon dioxide (SC-CO2) gel drying process was proposed to obtain CH scaffolds and, for the first time, the simultaneous elimination of unreacted glutaraldehyde (GTA), taking advantage of its solubility in supercritical mixtures. SC-CO2 gel dried crosslinked CH aerogels showed a nanofibrous structure characterized by an average diameter of about 100 nm. No collapse of the nanostructure was observed in the aerogels, due to the peculiarities of supercritical fluids (e.g., near zero surface tension). Moreover, crosslinked CH showed a thermally stable structure, as determined by TGA analysis. The hypothesis that a supercritical mixture is able to efficiently extract GTA residues entrapped in the gel matrix was also verified: negligible residues of GTA were found at the end of release experiments; in particular, at the best operating conditions, a GTA concentration equal to 0.013 ppm was detected. Therefore, the produced crosslinked CH aerogels can be effectively and safely used for TE applications.

Nanomedicine consists of the application of nanotechnologies in the medical field. In many nanomedical applications, supercritical fluids based processes represent the best potential choice, since they allow controlled fabrication of biological active nanoparticles, nanostructured microparticles, nanoporous/nanostructured materials. These products can be used to develop cell diagnostic kits, intracellular devices, engineered drug delivery systems, implantable materials and devices. This review is a critical analysis of the results reported in the literature on this fascinating and explosively growing field.

Energy density, safety, and simple and environmentally friendly preparation methods are very significant aspects in the realization of a compact supercapacitor. Herein we report the use of a supercritical CO

Scaffolds have been produced by supercritical CO2 drying of Poly-L-Lactid Acid (PLLA) gels loaded with micrometric fructose particles used as porogens. These structures show a microporous architecture generated by the voids left in the solid material by porogen leaching, while they maintain the nanostructure of the gel, consisting of a network of nanofilaments. These scaffolds have also been loaded with Hydroxyapatite (HA) nanoparticles, from 10 to 50% w/w with respect to the polymer, to improve the mechanical properties of the PLLA structure. Based on miscroscopic and mechanical considerations, we propose a parametric Finite Element Method (FEM) model of PLLA-HA composites that describes the microporous structure as a close-packing of equal spheres and the nanoscale structure as a space frame of isotropic curved fibers. The effect of HA on the mechanical properties of the scaffolds has been modeled on the basis of SEM images and by taking into consideration the formation of concentric cylinders of HA nanoparticles around PLLA nanofibers. Modeling analysis confirms that mechanical properties of these scaffolds depend on nanofibrous network connections and that bending is the major factor causing deformation of the network. The FEM model also takes into account the formation of HA multi-layer coating on some areas in the nanofiber network and its increase in thickness with HA percentage. The Young modulus tends to a plateau for HA percentages larger than 30% w/w and when the coverage of the nanofibers produced by HA nanoparticles reaches a loaded surface index of 0.14 in the FEM model.

Works in this area can be divided on whether the objective is to build an entire composite tissue unit or whether the objective is to assist the recreation of individual interfaces, such as improving integration of autografts with surrounding bone. The administration of active compounds to promote the anchoring of the interface lies on the hypothesis that it is possible to induce local restructuration of the specific tissue in the highly organized manner of the original junction. Its application requires complex procedures and relatively long times to produce interface reorganization. Techniques involving electrospinning have been applied to bone-to-tendon junction (BTJ) regeneration. Nevertheless, electrospun constructs are inherently discontinuous. Another approach potentially successful in BTJ regeneration is gel drying. The limit of this technique is the elimination of the organic solvents from the gel, avoiding the collapse of its nanostructure. Gel drying assisted by supercritical fluids has been recently proposed to eliminate the organic solvents in a simple and effective step, avoiding the structure collapse.

Cellulose acetate (CA)/graphene oxide (GO) nanocomposite membranes were generated by an assisted phase inversion process, based on the use of SC–CO2 as nonsolvent, operating at 200 bar and 40 °C; loadings of GO up to 9% w/w were tested. The structures maintained the cellular morphology, characteristics of CA membranes, also at the highest GO loadings used, with a porosity of about 80%, but the presence of GO influenced the pore sizes, that ranged between about 9 and 16 µm. The starting GO and the nanocomposite structures were characterized by the combination of various techniques that evidence as sulfur and chlorinated impurities, that were present in the starting GO material, were completely eliminated by the interaction with SC–CO2 during structures formation; moreover, a partial reduction of GO to graphene was also observed.

Energy density, safety, and simple and environmentally friendly preparation methods are very significant aspects in the realization of a compact supercapacitor. Herein we report the use of a supercritical CO2-assisted gel drying process (SC-CO2) for the preparation of porous electrodes containing dispersed graphene in a poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) binder membrane to sandwich in a new portable supercapacitor based on graphene oxide (GO). A GO loading of 60 wt.% was found to give the best combination of factors (porosity, wettability, mechanical and electrochemical properties). Cycling voltammetry and charge/discharge studies showed an excellent capacitance behaviour and stability in an ionic liquid electrolyte, suggesting SC-CO2 processing as a promising platform to produce highly bulky and porous films for supercapacitors. The supercapacitor device delivers a very high energy density of 79.2 Wh kg-1 at a power density of 0.23 KW kg-1 (current density 0.5 A g-1, specific capacitance 36.2 F g-1) while that of steel remains at 50.3 Wh kg-1 at a power density of 2.8 KW kg-1 (current density 6 A g-1, specific capacitance 23.5 F g-1).

The emerging next generation of engineered tissues is based on the development of loaded scaffolds containing bioactive molecules in order to control the cellular function or to interact on the surrounding tissues. Indeed, implantation of engineered biomaterials might cause local inflammation because of the host’s immune response; thereby, the use of anti-inflammatory agents, whether steroidal or nonsteroidal is required. One of the most important stages of tissue engineering is the design and the generation of a porous 3D structure, with high porosity, high interconnectivity and homogenous morphology. Various techniques have been reported in the literature for the fabrication of biodegradable scaffolds, but they suffer several limitations. In this study, for the first time, the possibility of generating 3D polymeric scaffolds loaded with an active compound by supercritical freeze extraction process is evaluated; this innovative process combines the advantages of the thermally induced phase separation process and of the supercritical carbon dioxide drying. Poly-l-lactid acid/ibuprofen composite scaffolds characterized by a 3D geometry, micrometric cellular structures and wrinkled pores walls have been obtained; moreover, homogeneous drug distribution and controlled release of the active principle have been assured.

Various techniques have been reported in the literature for the fabrication of biodegradable scaffolds; but, it is very difficult to obtain in the same structure macro, micro and nanostructural characteristics. In this work we developed a supercritical freeze extraction process (SFEP) for the formation of poly(l-lactic acid) (PLLA) scaffolds, that combines the advantages of thermally induced phase separation with those of supercritical drying. We processed solutions in chloroform of two PLLA molecular weights and at different polymer concentrations ranging between 5 and 20 % w/w. Supercritical drying was performed at 35 °Cand pressures ranging between 100 and 250 bar. 3-D scaffolds characterized by high porosity (between 88 and 97.5 %), with coexisting micro and nanometric morphology were obtained. Structures generated were characterized by pores ranging between 10 and 30 μm and with a wrinkled nanostructure of about 200 nm, superimposed on the internal pore surface, that could be useful for biomedical applications. A solvent residue lower than 5 ppm was also measured.