Production of mono and bilayer devices for wound dressing by coupling of electrospinning and supercritical impregnation techniques.

In this paper, electrospinning and supercritical impregnation were coupled to produce polyurethane fibrous membranes loaded with mesoglycan and lactoferrin. The proposed methodology allowed the production of three skin wound healing bilayer systems: a first system containing mesoglycan loaded through electrospinning and lactoferrin loaded by supercritical impregnation, a second system where the use of the two techniques was reversed, and a third sample where the drugs were both encapsulated through a one-step process. SEM analysis demonstrated the formation of microfibers with a homogeneous drug distribution. The highest loadings were 0.062 g/g for mesoglycan and 0.013 g/g for lactoferrin. Then, hydrophilicity and liquid retention analyses were carried out to evaluate the possibility of using the manufacturers as active patches. The kinetic profiles, obtained through in vitro tests conducted using a Franz diffusion cell, proved that the diffusion of the active drugs followed a double-step release before attaining the equilibrium after about 30 h. When the electrospun membranes were placed in contact with HUVEC, HaCaT, and BJ cell lines, as human endothelial cells, keratinocytes, and fibroblasts, respectively, no cytotoxic events were assessed. Finally, the capacity of the most promising system to promote the healing process was performed by carrying out scratch tests on HaCat cells.

Curcumin/Carrier Coprecipitation by Supercritical Antisolvent Route.

In this work, polyvinylpyrrolidone (PVP)- and ß-cyclodextrin (ß-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 ß-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/ ß-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 ß-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 ß-CD have an improved release rate.

Photocatalytic Degradation of Ceftriaxone Using TiO2 Coupled with ZnO Micronized by Supercritical Antisolvent Route.

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.

Supercritical impregnation of starch aerogels with quercetin: Fungistatic effect and release modelling with a compartmental model.

This work proposes the use of supercritical CO2 to impregnate starch (potato and corn) aerogels with quercetin for a potential fungistatic application. Starch aerogels were successfully produced with supercritical drying, but different results were found depending on the amylose/amylopectin ratio. A higher amount of amylose increases aerogels' specific surface area (with a structure with nanofibrils and nodes) due to the linear and amorphous character of this polymer, whereas a higher amount of amylopectin decreases this property until values of only 25 m2·g-1, obtaining an aerogel with a rough surface. These results were explained with XRD, thermogravimetric, and rheological results (triple step with two temperature sweeps and a time sweep and steady state analysis) concerning hydrogel formation. In fact, retrogradation step plays a more important role in hydrogel formation for a starch source with a higher amount of amylopectin due to an increase in the different polymers' interactions. Supercritical impregnation of quercetin on the aerogels was successfully performed (a loading around 0.30 % with respect to the amount of polymer), and in vitro results indicated that the aerogels produced a fungistatic effect on different types of fungi, but only in the first 12 h because the microorganisms adapted to the surrounding environment. Finally, a compartmental model was used to fit the drug release, which is controlled by quercetin aqueous solubility, indicating the main mass transfer resistances (mass transfer through aerogels was always around 500 min-1 and dissolution process mass transfer from 5·10-3 to 1.65·10-3 s-1) and how an increase in the specific surface area of the aerogels (in the case of corn aerogel) provided a stronger initial burst (70-80 % in 20 min). In fact, this initial burst release was mathematically related to a parameter, that varies from 0.178 to 0.036 depending on the aerogel composition. This study shows that starch aerogels can be impregnated with a hydrophobic compound with fungistatic effect by using supercritical CO2, modifying in addition the drug release by changing the native starch.

Supercritical Impregnation of Mesoglycan and Lactoferrin on Polyurethane Electrospun Fibers for Wound Healing Applications.

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.

Coprecipitation of Class II NSAIDs with Polymers for Oral Delivery.

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.

Supercritical Antisolvent Precipitation of Corticosteroids/ß-Cyclodextrin Inclusion Complexes.

In this study, corticosteroid-ß-cyclodextrin (ß-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 ß-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.

Supercritical Fluids and Nanoparticles in Cancer Therapy.

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.

Production of Mesoglycan/PCL Based Composites through Supercritical Impregnation.

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.

Zein Microparticles and Nanoparticles as Drug Delivery Systems.

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.

Production of carrier/antioxidant particles by Supercritical Assisted Atomization as an adjuvant treatment of the CoVID-19 pathology.

The 2019 coronavirus outbreak caused a global health emergency. Some therapeutic strategies for this pathology focus on natural compounds, such as flavonoids, because of their antimicrobial and antiviral properties. However, the therapeutic efficacy of these active compounds is limited by their low bioavailability. In this paper, composite systems consisting of the flavonoid and a carrier were produced by Supercritical Assisted Atomization to increase these compounds' dissolution rate. Luteolin, rutin, and naringenin were selected as model flavonoids, and hydroxypropyl-ß-cyclodextrin and polyvinylpyrrolidone were chosen as the carriers. Hydroxypropyl-ß-cyclodextrin was the most suitable carrier, in terms of recovery, morphology/size of the particles, and dissolution rate of the active compound. At the best operating conditions, the dissolution rate of the active principle is speeded for all the flavonoids: in particular, if compared to the virgin materials, it is 55.8 times faster for luteolin, 3.1 times faster for rutin and 3.4 times faster for naringenin.

Investigating the effects of supercritical antisolvent process and food models on antioxidant capacity, bioaccessibility and transepithelial transport of quercetin and rutin.

In the present study, the effects of the Supercritical Anti-Solvent (SAS) process and food models on the antioxidant capacity, bioaccessibility and transport dynamics of flavonol-loaded polyvinylpyrrolidone (PVP) based microparticles were investigated using a combined in vitro gastrointestinal digestion/Caco-2 cell culture model. SAS-processed and unprocessed flavonols were supplied in two different food models: 10% ethanol for an aqueous hydrophilic food simulant and 3% acetic acid for an acidic food simulant. The SAS processing of quercetin and rutin resulted in a much higher recovery of these bioactives as well as greater retention of antioxidant capacity after gastrointestinal digestion in both hydrophilic and acidic food models. The present study also demonstrates that SAS coprecipitation has a positive effect on the stability and transport of bioactives across the epithelial cell layer. It can be deduced from the results that the SAS process can be a useful method in pharmaceutical and nutraceutical applications with high stability, bioaccessibility, bioavailability and thus enhanced nutritional value.

Porous Aerogels and Adsorption of Pollutants from Water and Air: A Review.

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.

Supercritical Carbon Dioxide-Based Processes in Photocatalytic Applications.

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.

Contact Lenses as Ophthalmic Drug Delivery Systems: A Review.

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.

Polycaprolactone/polyethylene-glycol capsules made by injection molding: A drug release modeling.

Polycaprolactone (PCL)/Polyethylene-glycol (PEG) capsules are prepared by injection molding with the aim of producing Colon-specific Drug Delivery Systems (CDDS). PCL, being a gastroresistant polymer, is suitable for this kind of delivery; however, the release from PCL devices is too slow. For this reason, in this paper, different percentages of PEG (10, 20 and 30 w/w %) have been added to obtain blends able to modulate the release from PCL-based capsules. The drug release rate from PCL/PEG capsules increases with the PEG percentage; using PCL/PEG 70/30 w/w capsules, the drug release is suitable for CDDS. The experimental data have been modelled, accounting for three steps: the penetration of the release medium into the capsule, the drug dissolution in the release medium, and the drug migration from the capsule to the medium. The model accurately describes the data, showing a mass transfer coefficient strongly dependent on the PEG percentage.

Aerogels in drug delivery: From design to application.

Aerogels are the lightest processed solid materials on Earth and with the largest empty volume fraction in their structure. Composition versatility, modularity, and feasibility of industrial scale manufacturing are behind the fast emergence of aerogels in the drug delivery field. Compared to other 3D materials, the high porosity (interconnected mesopores) and high specific surface area of aerogels may allow faster loading of small-molecule drugs, less constrained access to inner regions of the matrix, and more efficient interactions of the biological milieu with the polymer matrix. Processing in supercritical CO2 medium for both aerogel production (drying) and drug loading (impregnation) has remarkable advantages such as absence of an oxidizing environment, clean manufacture, and easiness for the scale-up under good manufacturing practices. The aerogel solid skeleton dictates the chemical affinity to the different drugs, which in turn determines the loading efficiency and the release pattern. Aerogels can be used to increase the solubility of BCS Class II and IV drugs because the drug can be deposited in amorphous state onto the large surface area of the skeleton, which facilitates a rapid contact with the body fluids, dissolution, and release. Conversely, tuning the aerogel structure by functionalization with drug-binding moieties or stimuli-responsive components, application of coatings and incorporation of drug-loaded aerogels into other matrices may enable site-specific, stimuli-responsive, or prolonged drug release. The present review deals with last decade advances in aerogels for drug delivery. An special focus is paid first on the loading efficiency of active ingredients and release kinetics under biorelevant conditions. Subsequent sections deal with aerogels intended to address specific therapeutic demands. In addition to oral delivery, the physical properties of the aerogels appear to be very advantageous for mucosal administration routes, such as pulmonary, nasal, or transdermal. A specific section devoted to recent achievements in gene therapy and theranostics is also included. In the last section, scale up strategies and life cycle assessment are comprehensively addressed.

Formation of Rutin-ß-Cyclodextrin Inclusion Complexes by Supercritical Antisolvent Precipitation.

In this work, rutin (RUT)-ß-cyclodextrin (ß-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-ß-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-ß-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.

The Use of Poly(N-vinyl pyrrolidone) in the Delivery of Drugs: A Review.

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.

Eudragit: A Novel Carrier for Controlled Drug Delivery in Supercritical Antisolvent Coprecipitation.

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.