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Improper management of agro-industrial food waste represents a significant issue due to the associated uncontrolled release of climate-altering gases, total volatile organic compounds (TVOCs) and odours. The present study proposes an innovative solution to mitigate these emissions with supercritical carbon dioxide impregnation, employed to load R-Carvone into patches made from compostable pouches directly applied on two matrices: pork fat and tomato peel and seeds. Under optimized operating conditions (33 °C, 200 bar, 2 bar min-1) patches with 54 % R-Cav were produced, resulting in reduced CO2 and TVOCs emissions up to 200 and 0.2 ppm per gram, and reduced associated odour annoyance.

The global increase in energy demand requires a continuous search for renewable and clean alternative resources to fossil fuels. Hydrogen is emerging as a promising energy carrier for the future; its production via photocatalysis, driven by sunlight, can directly convert solar energy into a usable or storable energy resource. However, water splitting requires sacrificial agents or electron donors/hole scavengers, such as short-chain organic acids. This research explores the use of lactic acid as a source for photocatalytic hydrogen production, offering valuable alternatives for wastewater management and renewable energy production. This study employed the innovative supercritical antisolvent (SAS) technique to micronize the precursors of both the active phase (CeO2) and co-catalyst (CuO), ensuring rapid and complete solvent removal and size reduction of photocatalyst precursors. The prepared samples were characterized by field emission scanning electron microscopy (FESEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) analysis, Brunauer-Emmett-Teller (BET) analysis and thermogravimetric analysis (TGA). This study has shown that the micronization process resulted in a notable improvement in CeO2 photocatalytic activity, attributed to the reduction of the dimensions of the powders. Hydrogen production was equal to 3989 μmol L−1 for the SAS-produced photocatalyst while using a commercial CeO2 sample resulted in H2 production of 2519 μmol L−1. The enhanced photoactivity of CeO2-CuO composites was found to be related to the presence of CuO. The optimal CuO amount was equal to 0.5 wt%, determining a hydrogen production of 9313 μmol L−1 after 4 h of UV irradiation time. A photocatalytic test carried out with deuterated water (D2O) instead of distilled H2O demonstrated that hydrogen was preferentially produced from water splitting reaction, whereas lactic acid acted as a sacrificial agent being oxidized from positive holes photogenerated in the valence band of CuO.

Abstract Topical administration is the preferred route for the controlled release of active compounds since it reduces side effects typical of other administration methods. The use of polymer blends is a way to modulate drug release from a topical device. The blends ensure modulation of a wide range of properties, such as mechanical properties, water sorption, and degradation. This paper proposes blends of poly(lactide acid) (PLA), and Poly(butylene adipate‐co‐terephthalate) (PBAT), for the topical release of caffeine, a molecule with anti‐inflammatory, antioxidant, and anticellulite activities. PBAT/PLA blends are optimized for compatibility between the two polymers, mechanical properties, and drug release rate. Blends with a higher amount of PBAT show the best performance regarding polymer compatibility. The blends undergo supercritical CO2‐assisted caffeine impregnation. This process assures homogeneous dispersion of caffeine into the polymer matrix. The ratios 45/55 and 55/45 PBAT/PLA show the best performance in terms of caffeine release (complete caffeine release within 25 h). Caffeine is released into three steps: a burst effect due to the caffeine dispersed over the film surface, a slower release due to the caffeine dispersed in the polymer matrix, and a fast release due to the increase of polymer degradation rate induced by caffeine presence.

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In this work, polyvinylpyrrolidone (PVP)- and β-cyclodextrin (β-CD)-based composite powders containing curcumin (CURC) were obtained through the supercritical antisolvent (SAS) technique. Pressure, total concentration of CURC/carrier in dimethylsulfoxide, and CURC/carrier ratio effects on the morphology and size of the precipitated powders were investigated. Using PVP as the carrier, spherical particles with a mean diameter of 1.72 μm were obtained at 12.0 MPa, 20 mg/mL, and a CURC/PVP molar ratio equal to 1/2 mol/mol; using β-CD as the carrier, the optimal operating conditions were 9.0 MPa and 200 mg/mL; well-defined micrometric particles with mean diameters equal to 2.98 and 3.69 μm were obtained at molar ratios of 1/2 and 1/1 mol/mol, respectively. FT-IR spectra of CURC/ β-CD inclusion complexes and coprecipitated CURC/PVP powders revealed the presence of some peaks of the active compounds. The stoichiometry of the complexes evaluated through the Job method revealed that β-CD formed inclusion complexes with CURC at a molar ratio equal to 1/1. Dissolution profiles revealed that in comparison with the curve of the pure ingredient, the SAS-processed powders obtained using both PVP and β-CD have an improved release rate.

Heterogeneous photocatalysis is a promising technique for removing pollutants from water. In this work, supercritical antisolvent (SAS)-micronized ZnO (ZnOSAS) is coupled with commercial anatase TiO2 (PC50) to study the photocatalytic degradation of ceftriaxone under UV and visible light. Diffuse ultraviolet–visible reflectance (UV−vis DRS) measurement revealed that the presence of ZnO leads to a slight absorption in the visible region. Wide-angle X-ray diffraction (WAXD) analysis showed the presence of both ZnO wurtzite and TiO2 anatase crystalline phases in the composite. Photocatalytic tests proved that the activity of the ZnOSAS/PC50 composite is higher than that of commercial ZnO, SAS-micronized ZnO, and PC50, allowing complete ceftriaxone degradation under UV light after only 2 min of irradiation time. In contrast, about 90% of ceftriaxone degradation is achieved after 180 min of visible-light irradiation. The photocatalytic results for an experiment carried out in the presence of probe scavenger molecules for reactive oxygen species show that hydroxyl radicals and positive holes are both reactive species involved in the ceftriaxone photocatalytic degradation mechanism. Finally, reuse cycles of the ZnOsas/PC50 composite are performed, demonstrating the stability and recyclability of the photocatalyst.

In this study, corticosteroid–β-cyclodextrin (β-CD) inclusion complexes were prepared by using supercritical antisolvent (SAS) precipitation to enhance the dissolution rate of dexamethasone (DEX) and prednisolone (PRED), which are poorly water soluble drugs. The processing of the active principles in the absence of a carrier led to their almost complete extraction (the small amount of obtained material precipitates in the form of crystals). The coprecipitation of the ingredients in the presence of β-CD was investigated at different concentrations, pressures, and molar ratios. For both the corticosteroids, the optimized operating conditions were 40 °C, 120 bar, an equimolar ratio, and a concentration in DMSO of 20 mg/mL; these conditions led to the attainment of microparticles with mean diameters equal to 0.197 ± 0.180 μm and 0.131 ± 0.070 μm in the case of DEX and PRED, respectively. Job’s method confirmed the formation of inclusion complexes with a 1/1 mol/mol ratio. Compared to the pure ingredients, the obtained powders have an improved release rate, which is about three times faster in both cases. The release curves obtained under the best operating conditions were fitted using different models. The best fitting was obtained using the Weibull model, whose parameters are compatible with a combined release mechanism involving Fickian diffusion and controlled release.

Emerging contaminants are a significant issue in the environment. Photocatalysis is proposed as a solution for the degradation of pollutants contained in wastewater. In this work, ZnO-based photocatalysts have been produced and tested for the photocatalytic degradation of an antibiotic; specifically, ceftriaxone has been used as a model contaminant. Moreover, there is particular interest in combining small-size ZnO particles and β-cyclodextrin (β-CD), creating a hybrid photocatalyst. Zinc acetate (ZnAc) (subsequently calcinated into ZnO) and β-CD particles with a mean diameter of 0.086 and 0.38 µm, respectively, were obtained using the supercritical antisolvent process (SAS). The produced photocatalysts include combinations of commercial and micronized particles of ZnO and β-CD and commercial and micronized ZnO. All the samples were characterized through UV–Vis diffuse reflectance spectroscopy (DRS), and the band gap values were calculated. Raman and FT-IR measurements confirmed the presence of ZnO and the existence of functional groups due to the β-cyclodextrin and ZnO combination in the hybrid photocatalysts. Wide-angle X-ray diffraction patterns proved that wurtzite is the main crystalline phase for all hybrid photocatalytic systems. In the photocatalytic degradation tests, it was observed that all the photocatalytic systems exhibited 100% removal efficiency within a few minutes. However, the commercial ZnO/micronized β-CD hybrid system is the photocatalyst that shows the best performance; in fact, when using this hybrid system, ceftriaxone was entirely degraded in 1 min.

Fibrous membranes of thermoplastic polyurethane (TPU) were fabricated through a uni-axial electrospinning process. Fibers were then separately charged with two pharmacological agents, mesoglycan (MSG) and lactoferrin (LF), by supercritical CO2 impregnation. Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDS) analysis proved the formation of a micrometric structure with a homogeneous distribution of mesoglycan and lactoferrin. Besides, the degree of retention is calculated in four liquid media with different pHs. At the same time, angle contact analysis proved the formation of a hydrophobic membrane loaded with MSG and a hydrophilic LF-loaded one. The impregnation kinetics demonstrated a maximum loaded amount equal to 0.18 ± 0.20% and 0.07 ± 0.05% for MSG and LT, respectively. In vitro tests were performed using a Franz diffusion cell to simulate the contact with the human skin. The release of MSG reaches a plateau after about 28 h while LF release leveled off after 15 h. The in vitro compatibility of electrospun membranes has been evaluated on HaCaT and BJ cell lines, as human keratinocytes and fibroblasts, respectively. The reported data proved the potential application of fabricated membranes for wound healing.

Azo dyes are synthetic organic dyes used in the textile, leather, and paper industries. They pose environmental problems due to their toxic and persistent nature. The toxicity is due to the presence of azo groups in the dye molecule that can break down into aromatic amines, which are highly toxic to aquatic organisms and humans. Various treatment methods have been developed to remove azo dyes from wastewater. Conventional wastewater treatments have some drawbacks, such as high operating costs, long processing times, generation of sludge, and the formation of toxic by-products. For these reasons, a valid alternative is constituted by advanced oxidation processes. Good results have been obtained using heterogeneous photocatalysis and supercritical water oxidation. In the former method, a photocatalyst is in contact with wastewater, a suitable light activates the catalyst, and generated reactive oxygen species that react with pollutants through oxidative reactions to their complete mineralization; the latter involves pressurizing and heating wastewater to supercritical conditions in a reactor vessel, adding an oxidizing agent to the supercritical water, and allowing the mixture to react. In this review paper, works in the literature that deal with processing wastewater containing azo dyes through photocatalysts immobilized on macroscopic supports (structured photocatalysts) and the supercritical water oxidation technique have been critically analyzed. In particular, advancement in the formulation of structured photocatalysts for the degradation of azo dyes has been shown, underlying different important features, such as the type of support for the photoactive phase, reactor configuration, and photocatalytic efficiency in terms of dye degradation and photocatalyst stability. In the case of supercritical water oxidation, the main results regarding COD and TOC removal from wastewater containing azo dyes have been reported, taking into account the reactor type, operating pressure, and temperature, as well as the reaction time.

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently administered orally with modified-release formulations. The attainment of modified-release drugs is commonly achieved through the coprecipitation of the active principle with a biodegradable polymeric carrier in the form of micro or nanoparticles. In this review, some coprecipitation studies of three highly prescribed NSAIDs (in particular, ibuprofen, ketoprofen, and diclofenac sodium) have been analyzed. The techniques employed to micronize the powder, the polymers used, and the main results have been classified according to the type of release required in different categories, such as delayed, immediate, prolonged, sustained, and targeted release formulations. Indeed, depending on the pathology to be treated, it is possible to achieve specific therapeutic objectives, ensuring that the drug is released at a higher or lower dissolution rate (if compared to conventional drugs) and/or at a different time and/or in a specific site of action.

Nanoparticles are widely used in the pharmaceutical industry due to their high surface-to-volume ratio. Among the many techniques used to obtain nanoparticles, those based on supercritical fluids ensure reduced dimensions, narrow particle size distributions, and a very low or zero solvent residue in the powders. This review focuses on using supercritical carbon dioxide-based processes to obtain the nanoparticles of compounds used for the treatment or prevention of cancer. The scientific literature papers have been classified into two groups: nanoparticles consisting of a single active principle ingredient (API) and carrier/API nanopowders. Various supercritical carbon dioxide (scCO2) based techniques for obtaining the nanoparticles were considered, along with the operating conditions and advantages and disadvantages of each process.

The development of targeted therapies for wound repair is knowing a growing interest due to the increasing aging of the population and the incidence of chronic pathologies, mainly pressure ulcers. Among molecules recruiting cell populations and promoting the formation of new vital tissue, sodium mesoglycan (MSG) has been proven to be effective in wound healing. In this work, MSG impregnation of polymer matrices has been attempted by a supercritical carbon dioxide-based process. Polymeric matrices are composed of polycaprolactone blends, where water-soluble polymers, polyethylene glycol, polyvinyl pyrrolidone, gelatin, and thermoplastic starch, have been employed to modulate the MSG release, making the devices potentially suitable for topical administrations. Two different techniques have been used to obtain the films: the first one is compression molding, producing compact and continuous structures, and the second one is electrospinning, producing membrane-like designs. A higher amount of MSG can be loaded into the polymeric matrix in the membrane-like structures since, in these films, the impregnation process is faster than in the case of compression molded films, where the carbon dioxide has firstly diffused and then released the active molecule. The type of water-soluble polymer influences the drug release rate: the blend polycaprolactone-gelatin gives a prolonged release potentially suitable for topical administration.

In this work, ß-cyclodextrin (ß-CD) based inclusion complexes containing curcumin (CURC), a yellow pigment from Curcuma longa plants, were obtained through the Supercritical AntiSolvent (SAS) process. Curcumin has been widely used for its antioxidant, antimicrobial, antibiotic and antiviral properties. Recently, curcumin has been proposed as a potential treatment option for patients with coronavirus disease (CoVID-19). In order to protect the active compound, the supercritical antisolvent process was used, to induce the formation of inclusion complexes using ß-CD as the carrier. The effect of different parameters, such as pressure, overall concentration of solutes in the liquid solution, and CURC/ß-CD molar ratio, on the morphology and size of the composite particles, was investigated. Well-defined microparticles at 1/1 and 1/2 CURC/ß-CD molar ratios were produced. The dissolution rate curve of the obtained inclusion complexes was compared to the one of the unprocessed CURC.

Zein is a natural, biocompatible, and biodegradable polymer widely used in the pharmaceutical, biomedical, and packaging fields because of its low water vapor permeability, antibacterial activity, and hydrophobicity. It is a vegetal protein extracted from renewable resources (it is the major storage protein from corn). There has been growing attention to producing zein-based drug delivery systems in the recent years. Being a hydrophobic biopolymer, it is used in the controlled and targeted delivery of active principles. This review examines the present-day landscape of zein-based microparticles and nanoparticles, focusing on the different techniques used to obtain particles, the optimization of process parameters, advantages, disadvantages, and final applications.

Large amounts of food waste are produced each year. These residues require appropriate management to reduce their environmental impact and, at the same time, economic loss. However, this waste is still rich in compounds (e.g., colorants, antioxidants, polyphenols, fatty acids, vitamins, and proteins) that can find potential applications in food, pharmaceutical, and cosmetic industries. Conventional extraction techniques suffer some drawbacks when applied to the exploitation of food residues, including large amounts of polluting solvents, increased time of extraction, possible degradation of the active molecules during extraction, low yields, and reduced extraction selectivity. For these reasons, advanced extraction techniques have emerged in order to obtain efficient residue exploitation using more sustainable processes. In particular, performing extraction under high-pressure conditions, such as supercritical fluids and pressurized liquid extraction, offers several advantages for the extraction of bioactive molecules. These include the reduced use of toxic solvents, reduced extraction time, high selectivity, and the possibility of being applied in combination in a cascade of progressive extractions. In this review, an overview of high-pressure extraction techniques related to the recovery of high added value compounds from waste generated in food industries is presented and a critical discussion of the advantages and disadvantages of each process is reported. Furthermore, the possibility of combined multi-stage extractions, as well as economic and environmental aspects, are discussed in order to provide a complete overview of the topic.

Non-steroidal anti-inflammatory drugs are commonly prescribed for different diseases. A common problem for this wide class of drugs is their low bioavailability, strictly linked to their poor water solubility and, therefore, to their low dissolution rate. In the last years, many studies on novel Drug Delivery Systems (DDS) were performed to improve those drugs dissolution rate. An innovative approach consists in the adsorption of the active principle on a porous substrate. Polysaccharide aerogels are biodegradable and biocompatible; moreover, they are characterized by open pore structures and high surface areas. For these characteristics, they are particularly suitable to be loaded with an active ingredient. In this work, the environmental impacts of starch aerogel loaded with nimesulide, a widely employed nonsteroidal anti-inflammatory drug, using supercritical carbon dioxide impregnation were calculated, following a Life Cycle Assessment (LCA) approach. All the emissions to air, water and soil were reported to a 1.5 g starch aerogel tablet containing the therapeutic dose of nimesulide (100 mg). The life cycle assessment analysis was conducted using SimaPro 8.5.2 software, whereas the Ecoinvent 3.4 database and primary data were used for the life cycle inventory, according to the reference standard for LCA (i.e., ISO 14040-14044). A cradle-to-factory gate approach was followed; therefore, the system boundaries were set from the agricultural stages to the supercritical impregnation. The ReCiPe method was used to evaluate the effect of the tablet production on the midpoint and damage impact categories.

In this paper, the supercritical antisolvent (SAS) technique was proposed to coprecipitate ampicillin sodium (AMPI), an antibiotic chosen as the model drug, by using Eudragit L100-55 as the polymeric carrier. In the last years, supercritical carbon dioxide (scCO2) based techniques were frequently used to produce active principle/biopolymer composites with fast or controlled drug release. In this work, the Eudragit L100-55 micronization was studied and, as desired, the attainment of spherical microparticles of polymer with mean size in the range 1.64 - 1.99 µm was achieved. Then, SAS coprecipitation Eudragit/AMPI was investigated to verify the potential of Eudragit as the carrier for drug controlled delivery. Working at the best operating conditions, in terms of pressure (100 bar) and of overall concentration in the liquid solution (50 mg/mLDMSO), microspheres Eudragit/AMPI 20/1 and 10/1 w/w were obtained, with mean diameters of 2.52 µm and 1.53 µm, respectively. Release studies showed that the dissolution rate of ampicillin was prolonged 4 and 3 times, respectively in the case of SAS coprecipitated powders at 20/1 and 10/1 ratios. This outcome allowed to reduce the frequency of administration up to once a day, with fewer side effects due to antibiotic overdosing.

Semi-finished products are often used in the case of the high degree of perishability, like, for example, in the case of some fruits. The treatment of those fresh fruits allows the extension of foodstuffs’ shelf life, maintaining low the level at which microbial spoilage and deterioration reactions can occur. These semi-finished products are frequently used as starting materials by jams' and marmalades’ industries. The Southern Italy industry under study uses two different techniques to produce and preserve semi-finished peaches: one is based on low-pressure superheated steam drying with far-infrared radiation, and one on an ohmic aseptic treatment. The aim of this work is to use a Life Cycle Assessment (LCA) approach to compare the environmental emissions of those two different production and preservation techniques on two large scale plants. The environmental impacts were evaluated using a detailed LCA analysis, normalizing all the consumptions and emissions to the functional unit (one peaches’ kg on a dry basis). Data were analysed using SimaPro 8.5.2 software, whereas the Ecoinvent 3.4 database and information collected from the chosen industrial site were used for the life cycle inventory, according to the reference standard for LCA (i.e., ISO 14040 and 14044).

a-tocopherol (TOC), a poorly water-soluble vitamin, was impregnated using supercritical carbon dioxide in two different porous supports: an inorganic one (silica aerogel, SA) and a biopolymer one (maize starch aerogel, MSA). The composite systems can be used for the attainment of novel delivery systems with a rapid or controlled vitamin dissolution rate. TOC impregnation experiments on both the supports were carried out at a pressure of 15 MPa and a temperature of 60 °C. Impregnation equilibrium data were measured and represented as isotherms, whereas impregnation kinetic data were obtained by determining the TOC uptake on the two supports at various times. The TOC/aerogel composites were characterized by FESEM analysis and specific surface area determination. To study the properties of the adsorbed aerogels, as vitamin delivery systems, in vitro dissolution tests were performed. The dissolution rates of TOC charged in silica aerogel or maize starch aerogel using phosphate buffered saline solution (PBS) were compared with the one of the unprocessed vitamin.

In this paper, composite systems containing curcumin (CUR) were prepared through supercritical-assisted atomization (SAA), using different carriers. Curcumin is particularly interesting in the pharmaceutical and nutraceutical fields for its antioxidant, antitumoral, and anti-inflammatory properties. However, its therapeutic effect on human health is restricted by its poor water solubility and low dissolution rate, limiting its absorption after its oral administration. To increase the dissolution rate and then the bioavailability of the active compound, CUR was coprecipitated with polymeric, i.e., polyvinylpyrrolidone (PVP) and dextran (DXT), and not polymeric, i.e., hydroxypropyl-β-cyclodextrin (HP-β-CD), carriers. The effects of some operating parameters, namely the concentration of solutes in solution and the active compound/carrier ratio, on the morphology and the particle size distribution of the powders were investigated. Submicrometric particles were produced with all the carriers. Under the best operating conditions, the mean diameters ± standard deviation were equal to 0.69 ± 0.20 μm, 0.40 ± 0.13 μm, and 0.81 ± 0.25 μm for PVP/CUR, DXT/CUR, and HP-β-CD/CUR, respectively. CUR dissolution rates from coprecipitated particles were significantly increased in the case of all the carriers. Therefore, the results are exciting from a pharmaceutical and nutraceutical point of view, to produce supplements containing curcumin, but assuring a high dissolution rate and bioavailability and, consequently, a more effective therapeutic effect.

Aerogels are open, three-dimensional, porous materials characterized by outstanding properties, such as low density, high porosity, and high surface area. They have been used in various fields as adsorbents, catalysts, materials for thermal insulation, or matrices for drug delivery. Aerogels have been successfully used for environmental applications to eliminate toxic and harmful substances—such as metal ions or organic dyes—contained in wastewater, and pollutants—including aromatic or oxygenated volatile organic compounds (VOCs)—contained in the air. This updated review on the use of different aerogels—for instance, graphene oxide-, cellulose-, chitosan-, and silica-based aerogels—provides information on their various applications in removing pollutants, the results obtained, and potential future developments.

Conventional methods generally used to synthesize heterogeneous photocatalysts have some drawbacks, mainly the difficult control/preservation of catalysts’ morphology, size or structure, which strongly affect the photocatalytic activity. Supercritical carbon dioxide (scCO2)-assisted techniques have recently been shown to be a promising approach to overcome these limitations, which are still a challenge. In addition, compared to traditional methods, these innovative techniques permit the synthesis of high-performance photocatalysts by reducing the use of toxic and polluting solvents and, consequently, the environmental impact of long-term catalyst preparation. Specifically, the versatility of scCO2 allows to prepare catalysts with different structures (e.g., nanoparticles or metal-loaded supports) by several supercritical processes for the photocatalytic degradation of various compounds. This is the first updated review on the use of scCO2-assisted techniques for photocatalytic applications. We hope this review provides useful information on different approaches and future perspectives.

Ophthalmic drugs used for the treatment of various ocular diseases are commonly administered by eye drops. However, due to anatomical and physiological factors, there is a low bioavailability of the active principle. In order to increase the drug residence time on the cornea to adequate levels, therapeutic contact lenses have recently been proposed. The polymeric support that constitutes the contact lens is loaded with the drug; in this way, there is a direct and effective pharmacological action on the target organ, promoting a prolonged release of the active principle. The incorporation of ophthalmic drugs into contact lenses can be performed by different techniques; nowadays, the soaking method is mainly employed. To improve the therapeutic performance of drug-loaded contact lenses, innovative methods have recently been proposed, including the impregnation with supercritical carbon dioxide. This updated review of therapeutic contact lenses production and application provides useful information on the most effective preparation methodologies, recent achievements and future perspectives.

Many active ingredients currently prescribed show limited therapeutic efficacy, mainly due to their dissolution rate inadequate to treat the pathology of interest. A large drug particle size creates an additional problem if a specific site of action in the human body has to be reached. For this reason, active ingredient size reduction using micronization/nanonization techniques is a valid approach to improve the efficacy of active compounds. Supercritical carbon-dioxide-assisted technologies enable the production of different morphologies of different sizes, including nanoparticles and nanocrystals, by modulating operating conditions. Supercritical fluid-based processes have numerous advantages over techniques conventionally employed to produce nanosized particles or crystals, such as reduced use of toxic solvents, which are completely removed from the final product, ensuring safety for patients. Active compounds can be processed alone by supercritical techniques, although polymeric carriers are often added as stabilizers, to control the drug release on the basis of the desired therapeutic effect, as well as to improve drug processability with the chosen technology. This updated review on the application of supercritical micronization/nanonization techniques in the pharmaceutical field aims at highlighting the most effective current results, operating conditions, advantages, and limitations, providing future perspectives.

In this work, rutin (RUT)–β-cyclodextrin (β-CD) inclusion complexes are prepared by Supercritical AntiSolvent (SAS) precipitation. Well-defined composite microparticles are obtained at guest:host ratios equal to 1:2 and 1:1 mol:mol. The dimensions of composite particles range between 1.45 ± 0.88 µm and 7.94 ± 2.12 µm. The formation of RUT–β-CD inclusion complexes has been proved by different analyses, including Fourier transform infrared spectroscopy, Differential Scanning Calorimetry, X-ray diffraction, and UV-vis spectroscopy. The dissolution tests reveal a significant improvement in the release rate of RUT from inclusion complexes. Indeed, compared to the unprocessed RUT, the dissolution rate is about 3.9 and 2.4 times faster in the case of the complexes RUT–β-CD 1:2 and 1:1 mol:mol, respectively. From a pharmaceutical/nutraceutical point of view, CD-based inclusion complexes allow the reduction of the polymer amount in the SAS composite formulations.

Polyvinylpyrrolidone (PVP) is a hydrophilic polymer widely employed as a carrier in the pharmaceutical, biomedical, and nutraceutical fields. Up to now, several PVP-based systems have been developed to deliver different active principles, of both natural and synthetic origin. Various formulations and morphologies have been proposed using PVP, including microparticles and nanoparticles, fibers, hydrogels, tablets, and films. Its versatility and peculiar properties make PVP one of the most suitable and promising polymers for the development of new pharmaceutical forms. This review highlights the role of PVP in drug delivery, focusing on the different morphologies proposed for different polymer/active compound formulations. It also provides detailed information on active principles and used technologies, optimized process parameters, advantages, disadvantages, and final applications.

In this work, the supercritical antisolvent (SAS) process was used to coprecipitate Eudragit L100-55 (EUD) with diclofenac (DICLO) and theophylline (THEOP), with the aim of obtaining composite microparticles with a prolonged drug release for oral delivery. Working at the optimized conditions in terms of pressure and overall concentration in the liquid solution (10.0 MPa and 50 mg/mL), microparticles of EUD/DICLO 20/1 and 10/1 w/w were produced with a mean size of 2.92 µm and 1.53 µm, respectively. For the system EUD/THEOP, well-defined spherical microspheres with a mean diameter ranging from 3.75 µm and 5.93 µm were produced at 12.0 MPa. The produced composite systems were characterized by various techniques, such as scanning electron microscopy, differential scanning calorimetry, X-ray microanalysis, FT-IR and UV−vis spectroscopy. Dissolution studies showed the potential of EUD to prolong the drug release, significantly, up to a few days.

Cellulose acetate (CA) is a very versatile biocompatible polymer used in various industrial sectors. Therefore, depending on the application, different morphologies are required. Different processes at industrial scale are commonly employed to obtain CA micro or nanoparticles (discontinuous structures) or CA membranes (continuous structures with discontinuities). In this work, two supercritical carbon dioxide (scCO2) based techniques, such as the semi-continuous supercritical antisolvent process (SAS) and the supercritical fluid phase inversion process, in which scCO2 plays the role of antisolvent, were employed. Varying the kind of organic solvent used to prepare the polymeric solution, the polymer concentration, and operating pressure and temperature, it was possible to tune the characteristics of the obtained material. In particular, using acetone as the organic solvent, filaments constituted by nanoparticles, expanded microparticles, nanoparticles with a mean diameter lower than 80 nm, and microporous membranes were obtained, varying the operating conditions. The attainment of spherical micron-sized particles was instead achieved using a mixture of acetone and DMSO as the organic solvent. Therefore, the versatility of the supercritical carbon dioxide-based techniques has been confirmed, and it was possible to obtain, using a single experimental plant, various morphologies of cellulose acetate (with controllable particles’ or pores’ diameters) by varying the operating conditions.

We have recently demonstrated that mesoglycan, a fibrinolytic compound, may be a promising pro-healing drug for skin wound repair. We showed that mesoglycan induces migration, invasion, early differentiation, and translocation to the membrane of keratinocytes, as well as the secretion of annexin A1 (ANXA1), further involved in keratinocytes activation. These events are triggered by the syndecan-4 (SDC4)/PKCα pathway. SDC4 also participates to the formation and secretion of microvesicles (EVs) which may contribute to wound healing. EVs were isolated from HaCaT cells, as human immortalized keratinocytes, and then characterised by Western blotting, Field Emission-Scanning Electron Microscopy, and Dynamic Light Scattering. Their autocrine effects were investigated by Wound-Healing/invasion assays and confocal microscopy to analyse cell motility and differentiation, respectively. Here, we found that the mesoglycan increased the release of EVs which amplify its same effects. ANXA1 contained in the microvesicles is able to promote keratinocytes motility and differentiation by acting on Formyl Peptide Receptors (FPRs). Thus, the extracellular form of ANXA1 may be considered as a link to intensify the effects of mesoglycan. In this study, for the first time, we have identified an interesting autocrine loop ANXA1/EVs/FPRs in human keratinocytes, induced by mesoglycan.

In this work, the synthesis of zinc oxide (ZnO) photocatalyst from thermal decomposition of zinc acetate (ZnAc) nanoparticles obtained by supercritical antisolvent (SAS) precipitation was investigated. The optimization of calcination conditions of the SAS ZnAc was carried out, studying the effect of temperature (in the range 300–600 °C) on the production of ZnO nanoparticles. In particular, it was demonstrated that the organic residues in ZnO and its particle size, thus the specific surface area, strongly affect the photocatalytic performances. SAS micronization of ZnAc produces regular nanoparticles with a mean diameter of about 54.5 ± 11.5 nm, whereas unprocessed ZnAc is characterized by very large crystals. The experimental results evidenced that ZnAc prepared by SAS process calcined at 500 °C showed a regular nanometric structure (mean diameter: 65.0 ± 14.5 nm) and was revealed to be the best choice for the photocatalytic removal of crystal violet dye (CV). In fact, the photocatalytic activity performances of ZnO nanoparticles prepared by this route were higher with respect to that of ZnO from unprocessed ZnAc calcined at 500 °C (which is characterized by irregular tetrapods with mean size 181.1 ± 65.5 nm). The optimized photocatalyst was able to assure the complete CV decolorization in 60 min of UV irradiation time and a mineralization degree higher than 90% after 120 min of treatment time.

Pancreatic Cancer (PC) is one of the most aggressive malignancies worldwide. As annexin A1 (ANXA1) is implicated in the establishment of tumour metastasis, the role of the protein in PC progression as a component of extracellular vesicles (EVs) has been investigated. EVs were isolated from wild type (WT) and ANXA1 knock-out (KO) PC cells and then characterised by multiple approaches including Western blotting, Field Emission-Scanning Electron Microscopy, and Dynamic Light Scattering. The effects of ANXA1 on tumour aggressiveness were investigated by Wound-Healing and invasion assays and microscopic analysis of the Epithelial to Mesenchymal Transition (EMT). The role of ANXA1 on angiogenesis was also examined in endothelial cells, using similar approaches. We found that WT cells released more EVs enriched in exosomes than those from cells lacking ANXA1. Notably, ANXA1 KO cells recovered their metastatic potential only when treated by WT EVs as they underwent EMT and a significant increase of motility. Similarly, human umbilical vein endothelial cells (HUVEC) migrated and invaded more rapidly when treated by WT EVs whereas ANXA1 KO EVs weakly induced angiogenesis. This study suggests that EVs-related ANXA1 is able to promote cell migration, invasion, and angiogenesis, confirming the relevance of this protein in PC progression.