Supercritical CO2 Impregnation Research Articles

Supercritical CO2 impregnation of pink pepper essential oil in gelatin-siloxane cryogel for biomedical applications

The supercritical CO2 impregnation of pink pepper essential oil (EO) can bring its bioactive properties to a biomaterial in a green approach, making it multifunctional. Aiming to obtain a gelatin-siloxane cryogel loaded with pink pepper EO for biomedical applications and to understand the impact of the impregnation conditions, gelatin was crosslinked with (3-glycidoxypropyl)trimethoxysilane and lyophilized, and the impregnation was studied using a design of experiments with conditions from 10 to 30 MPa and 35–60 °C. The cryogel synthesis was confirmed by FTIR, %gel and TGA. Its biocompatibility was demonstrated through SEM, water uptake and cytotoxicity studies. It was shown that, due to the influence on the solubility of the EO in scCO2, varying pressure and temperature influences the impregnation, which showed {20 MPa; 35 °C} as its best condition. Therefore, a cryogel suitable for implantation with potential to reduce side effects related with infection and inflammation was obtained.

Functionalization of chitosan films using essential oils by supercritical CO2 impregnation method for various applications

Herein, chitosan films obtained by different approaches were functionalized with essential oils, i.e. mentha, clove, and cinnamon, by Supercritical Solvent Impregnation method to impart antioxidant and antimicrobial activity. The films were prepared from solutions with two different polymer concentrations (1 and 2.5 wt%) following three methodologies: casting and then drying at air (25 °C, 39 % relative humidity), casting and drying at 60 °C in humid conditions (82 % relativity humidity) and casting and water elimination by a freeze-drying process. The films were, then, characterized by scanning electron microscopy and X-ray diffraction, proving that the thickness, porosity, and crystallinity of the films are highly dependent on the preparation method. These structural variations affected the impregnation of essential oils by supercritical fluids, in terms of the amount and composition of the active compounds. Subsequently, yellowness, antioxidant and antimicrobial properties of the impregnated films were evaluated. The results demonstrated that the impregnated films retained high concentration of essential oils, especially the films impregnated with clove and produced by the freeze-drying process due to their higher porosity and lower crystallinity. These films also exhibited superior antimicrobial activity against Gram-positive and Gram-negative bacteria in comparison with the other two analyzed preparation methods.

Drug loading of bioresorbable suture threads by supercritical CO2 impregnation: a proof of concept for industrial scale-up

Supercritical CO2 (scCO2) impregnation emerged as a suitable technique to load thermosensitive drugs in polymeric devices thanks to mild process temperatures, the absence of toxic solvents and the easy removal of residual solvent through depressurization. This technique has been successfully tested at lab scale but few attempts to scale-up the process are reported. This work aims at filling this gap by performing a scCO2 impregnation at pilot scale of bioresorbable suture threads with ketoprofen. The process led to low drug loading values (0.2 – 0.8%) and to a very fast eluting rate, suggesting that they can be suitable when an immediate burst release is needed. Experiments were complemented by a multiscale mathematical modeling to better rationalize the outcomes. This work constitutes a proof of concept for a possible strategy to perform the scale-up of scCO2-assisted drug loading and highlighted some aspects to be addressed for future developments.

Supercritical CO2-impregnation of clove extract in PLLA films: assessing process parameter effects on extract loading and composition

The supercritical carbon dioxide (scCO2) impregnation of clove extract (CE) into poly(L-lactic acid) (PLLA) films was explored with varying pressure (10–30MPa) and temperature (35–60 °C), achieving high clove extract loadings (CL) (12.3 - 44.4%). In all conditions, impregnated extracts exhibited elevated eugenol content and reduced content of eugenyl acetate, β-caryophyllene, and α-humulene, compared to crude extract, showing the selective character of the process. Strong eugenol/PLLA affinity demonstrated by solubility parameters and hydrogen bonds permitted its effective impregnation. Eugenol significantly plasticized PLLA film, resulting in alterations in its microstructure, including increased crystallinity and smaller crystals. A CL of 23.8% maintained a dense and uniform structure of PLLA, while 44.4% induced a thick microporous layer on the surfaces. CE-impregnated PLLA, rich in eugenol, is promising for developing active food packaging and extract-releasing medical.

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.

Development of PLA suture materials by extrusion, electrospinning and supercritical CO2 impregnation of ibuprofen and naproxen

Suture materials based on poly (lactic acid) (PLA) were developed by means of two different methods: extrusion and electrospinning, which were followed by a supercritical CO2 impregnation treatment. Both suture materials obtained by these techniques were impregnated with naproxen and ibuprofen using supercritical CO2 as impregnation medium. The impregnation assays were carried out at two different pressures (12 and 15 MPa), a temperature of 40 °C and, a depressurization rate of 1 MPa/min. Depending on the drugs incorporated into the suture materials, the concentrations varied from 5.60 to 26.73 wt%. The addition of both drugs and, the preparation process itself caused different changes in the structural and thermal properties of the final suture materials. Finally, tests to quantify the kinetic release of both drugs were carried out in vitro by using a Franz diffusion cell, obtaining the concentration profiles of delivered compounds as a function of the time.

Supercritical CO2 Impregnation of Clove Extract in Polycarbonate: Effects of Operational Conditions on the Loading and Composition

The development of active packaging for food storage containers is possible through impregnation of natural extracts by supercritical CO2-assisted impregnation processes. The challenge of scCO2-impregnation of natural extracts is to control the total loading and to ensure that the composition of the loaded extract may preserve the properties of the crude extract. This study aimed at investigating the scCO2-impregnation of clove extract (CE) in polycarbonate (PC) to develop antibacterial packaging. A design of experiments was applied to evaluate the influences of temperature (35–60 °C) and pressure (10–30 MPa) on the clove loading (CL%) and on the composition of the loaded extract. The CL% ranged from 6.8 to 18.5%, and the highest CL% was reached at 60 °C and 10 MPa. The composition of the impregnated extract was dependent on the impregnation conditions, and it differed from the crude extract, being richer in eugenol (81.31–86.28% compared to 70.06 in the crude extract). Differential scanning calorimetry showed a high plasticizing effect of CE on PC, and high CL% led to the cracking of the PC surface. Due to the high loading of eugenol, which is responsible for the antibacterial properties of the CE, the impregnated PC is promising for producing antibacterial food containers.

Supercritical CO2 Impregnation of Thymol in Thermoplastic Starch-Based Blends: Chemico-Physical Properties and Release Kinetics.

The aim of the present study was to investigate starch-based materials, prepared in an environmentally friendly way and from renewable resources, suitable for the development of biodegradable active food packaging. For this purpose, a bioactive compound (thymol) was incorporated into thermoplastic starch (TPS) and a TPS blend with poly (ε-caprolactone) (TPS–PCL) by the supercritical CO2 (scCO2) impregnation process. Impregnation experiments with scCO2 were carried out at a pressure of 30 MPa and temperatures in the range of 40–100 °C during 1 to 20 h. The structural, morphological, and thermal properties of the obtained materials were comprehensively evaluated. Bioactive component release kinetic studies were performed in water at 6 °C and 25 °C. It was shown that the scCO2 impregnation process could be successfully employed for thymol loading into TPS and TPS–PCL. The process was significantly influenced by the operating temperature and time as well as content of PCL. The samples showed a controlled release of thymol within seven days with a higher amount of released thymol from the TPS–PCL blend. The obtained materials are solvent-free and release the bioactive component in a controlled manner.

Inclusion of Natural Antioxidants of Mango Leaves in Porous Ceramic Matrices by Supercritical CO2 Impregnation.

Mango is one of the most important, medicinal tropical plants in the world from an economic point of view due to the presence of effective bioactive substances as co-products in its leaves. The aim of this work was to enhance the impregnation of natural antioxidants from mango leaves into a porous ceramic matrix. The effects of pressure, temperature, impregnation time, concentration of the extract and different porous silica on impregnation of phenolic compounds and antioxidant activity were analyzed. The volume of the pressurized fluid extract and amount of porous ceramic matrix remained constant. The best impregnation conditions were obtained at 6 h, 300 bar, 60 mg/mL, 35 °C and with MSU-H porous silica. The results indicated that increasing the pressure, concentration of the extract and temperature during impregnation with phenolic compounds such as gallic acid and iriflophenone 3-C (2-O-p-hydroxybenzolyl)-β-D-glucoside increased the antioxidant activity and the amount of total phenols.

Role of supercritical CO2 impregnation variables on β-carotene loading into corn starch aerogel particles

β-carotene is a natural dye with antioxidant and provitamin A activities, which has essential roles in human health. However, its direct use in food products is unviable since it is susceptible to oxidation, easily isomerization under light, heat or acids, and has low water solubility and oral bioavailability. To address this issue, this work reports, for the first time, the impregnation of β-carotene into corn starch aerogels using supercritical carbon dioxide (sc-CO2). The aerogel particles were produced by the emulsion-gelation method, dried by sc-CO2 and loaded with β-carotene by sc-CO2 impregnation. The impacts of pressure (15 and 30 MPa), temperature (40 and 60 °C), average depressurization rate (0.25–2.61 MPa/min), and cycles (1−4) were investigated on loading. Excepting depressurization rate, all variables played fundamental roles in loading, reaching a maximum of 0.96 mg β-carotene/g aerogel (30 MPa, 40 °C, 0.40 MPa/min, four cycles).

Hydrolysed collagen as carrier material for particle formation via supercritical CO2 impregnation

This work investigated hydrolysed collagen (HC) powder as carrier material for particle formation via supercritical CO2 impregnation. HC solubility and volumetric expansion in supercritical CO2 (ρ: 605.8–834.8 g/L) were measured. Formation of HC particles loaded with lycopene dispersed in sunflower oil (LSO) (HC-LSO) using supercritical CO2 at 100–140 bar and 40–50 °C and HC/LSO ratios of 4:1–10:1 (w/w) was studied. HC had constant solubility (0.5–0.6 g/kg CO2) and no volumetric expansion was visibly observed. HC-LSO had similar spherical morphology, size distribution, and loading capacity (0.025 g of LSO/g of HC) between treatments. HC-LSO formed with HC/LSO ratio of 10:1 (w/w) stand out for their low agglomeration. Since HC showed low interaction with supercritical CO2 under different conditions and preserved its powder appearance after impregnation with LSO, it is suggested to be used as carrier of lipophilic bioactive compounds in particle formation via supercritical CO2 impregnation at moderate temperature (40–50 °C).

Supercritical CO2 impregnation approach for enhancing dissolution of fenofibrate by adsorption onto high-surface area carriers

Hydrophobic drugs pose a challenge to pharmaceutical oral dosage forms because their low dissolution reduced bioavailability. In this study, we developed different strategies to adsorb fenofibrate (FB), a BCS II drug, onto high-surface-area carriers (Ae200) to enhance its dissolution. As compared to physical mixing and spray drying, physical adsorption and supercritical fluid methods showed the highest dissolution rates (over 80% in 30 min and over 90% in 60 min) with the highest surface area values. Among the two best methods, supercritical solvent impregnation technique (SCF1) offered better dissolution behavior, attributed to the FB physical state transition from crystalline to amorphous. This improvement suggests the potential of the SCF1 in the development of hydrophobic drugs.

Supercritical CO2 impregnation of caffeine in biopolymer films to produce anti-cellulite devices

The present work focuses on the production of topical anti-cellulite devices through a supercritical one-step process consisting of the polymer foaming and impregnation of caffeine into PLA/PBAT/CaCO3 films to obtain a biocompatible and biodegradable patch. Field Emission Scanning Electron Microscopy analysis revealed that porosities were formed in the polymeric support when in contact with the supercritical CO2. Atomic force microscopy revealed the presence of caffeine on the polymer surface in the form of needles. The impregnation kinetics determined at 17.0 MPa showed an increase in caffeine loadings with the contact time (up to 16.5% and 23.0% wcaffeine/wfilm at 40 °C and 35 °C, respectively), corresponding to higher caffeine loadings than the ones contained in commercial products (about 3%). The release of caffeine was simulated by UV–vis spectrophotometry: pure caffeine dissolved instantly in the dissolution medium, whereas its release was prolonged up to 2 days when it was impregnated within the PLA/PBAT/CaCO3 film.

Aspirin-Loaded Polymeric Films for Drug Delivery Systems: Comparison between Soaking and Supercritical CO2 Impregnation.

Polymeric implants loaded with drugs can overcome the disadvantages of oral or injection drug administration and deliver the drug locally. Several methods can load drugs into polymers. Herein, soaking and supercritical CO2 (scCO2) impregnation methods were employed to load aspirin into poly(l-lactic acid) (PLLA) and linear low-density polyethylene (LLDPE). Higher drug loadings (DL) were achieved with scCO2 impregnation compared to soaking and in a shorter time (3.4 ± 0.8 vs. 1.3 ± 0.4% for PLLA; and 0.4 ± 0.5 vs. 0.6 ± 0.5% for LLDPE), due to the higher swelling capacity of CO2. The higher affinity of aspirin explained the higher DL in PLLA than in LLDPE. Residual solvent was detected in LLDPE prepared by soaking, but within the FDA concentration limits. The solvents used in both methods acted as plasticizers and increased PLLA crystallinity. PLLA impregnated with aspirin exhibited faster hydrolysis in vitro due to the catalytic effect of aspirin. Finally, PLLA impregnated by soaking showed a burst release because of aspirin crystals on the PLLA surface, and released 100% of aspirin within 60 days, whereas the PLLA prepared with scCO2 released 60% after 74 days by diffusion and PLLA erosion. Hence, the scCO2 impregnation method is adequate for higher aspirin loadings and prolonged drug release.

Piroxicam Loading onto Mesoporous Silicas by Supercritical CO2 Impregnation.

Piroxicam (PRX) is a commonly prescribed nonsteroidal anti-inflammatory drug. Its efficacy, however, is partially limited by its low water solubility. In recent years, different studies have tackled this problem and have suggested delivering PRX through solid dispersions. All these strategies, however, involve the use of potentially harmful solvents for the loading procedure. Since piroxicam is soluble in supercritical CO2 (scCO2), the present study aims, for the first time, to adsorb PRX onto mesoporous silica using scCO2, which is known to be a safer and greener technique compared to the organic solvent-based ones. For comparison, PRX is also loaded by adsorption from solution and incipient wetness impregnation using ethanol as solvent. Two different commercial mesoporous silicas are used (SBA-15 and Grace Syloid® XDP), which differ in porosity order and surface silanol population. Physico-chemical analyses show that the most promising results are obtained through scCO2, which yields the amorphization of PRX, whereas some crystallization occurs in the case of adsorption from solution and IWI. The highest loading of PRX by scCO2 is obtained in SBA-15 (15 wt.%), where molecule distribution appears homogeneous, with very limited pore blocking.

V2O5/vertically-aligned carbon nanotubes as negative electrode for asymmetric supercapacitor in neutral aqueous electrolyte

Development of aqueous asymmetric supercapacitors (ASCs) is often limited by low specific capacitance of negative electrodes. Herein, a composite electrode with tiny vanadium pentoxide (V2O5) nanoparticles homogeneously decorated in vertically-aligned carbon nanotube arrays (VACNTs) is prepared by supercritical CO2 impregnation and subsequent annealing, and used as binder-free negative electrode for aqueous ASCs. Owing to its unique three-dimensional (3D) hierarchical nanostructure, the V2O5/VACNTs (VN) electrodes exhibit an ideal specific capacitance of 284 F g−1 in the potential range of −1.1 to 0 V vs SCE at 2 A g−1 and outstanding cycling stability in the Na2SO4 aqueous solution. An aqueous ASC device possessing wide potential range of 1.7 V was constructed with pure VACNTs and VN-350 as the positive and negative electrodes, respectively. The ASC delivers a high energy density of 32.3 Wh kg−1 at a power density of 118 W kg−1 and satisfactory cycling life with capacitance retention of 76% after 5000 cycles.

Water free incorporation of shark liver oil into starch microparticles by supercriticalCO2impregnation at low temperature

AbstractShark liver oil (SLO), rich in squalene, was incorporated into modified starch microparticles (MSMs) by supercritical CO2. This polyunsaturated triterpene presents antitumor and antioxidant activities and, due to the high level of unsaturation in the molecule, it is vulnerable to oxidative attack. This research therefore contributes to the development of methods for impregnating such oil into MSM in order to increase the oil's oxidation stability and prevent its degradation in order to facilitate its use in mixtures with inputs for drugs, foods, and cosmetic. To form SLO‐incorporated MSM, a physical mixture composed of 44% of two MSM with different degrees of hydrophobicity, 11% SLO, 1% lecithin, and 44% ethanol were treated with supercritical CO2at 120 bar, 40, and 60°C. The SLO‐incorporated MSM preserved MSM morphology and exhibited good incorporation of SLO (74–82%), a high degree of solubilization in water (78–86%), and a low hygroscopicity (4–9%). Stability evaluation revealed that the SLO‐incorporated MSM of Purity Gum Ultra that was formed at 60°C preserved 44% of the initial squalene content. Accordingly, supercritical impregnation represents a practical alternative for SLO impregnation since it is a quick method that does not use water in its formulation and can be done at low temperature.Practical ApplicationsThe improvement of drug and food inputs that are thermosensitive in nature and/or of low polarity can be produced by using low‐cost wall material that can make the process more cost effective and more accessible. Particle formation by supercritical CO2impregnation is a green and nonaggressive process for bioactive compounds that allows the design of innovative food products. Moreover, the fact that the use of modified starches for wall materials, which are already used safely by the food and pharmaceutical industries, makes the process and derived products more reliable. In this sense, the incorporation of shark liver oil (rich is squalene) in modified starch microparticles by supercritical impregnation could be a practical alternative for powdered food industries.

Synergistic effects in the simultaneous supercritical CO2 impregnation of two compounds into poly(L- lactic acid) and polyethylene

The present work investigated the specific phenomena involved in the simultaneous scCO2 impregnation of two compounds in polymers. For this purpose, poly(L- lactic acid) and linear low density polyethylene were impregnated with three different combinations of two compounds among aspirin, ketoprofen and carvone. The loadings were studied regarding the effect of the impregnation conditions ({60 °C; 9 MPa} and {80 °C; 30 MPa}), the polymer/compound and the scCO2/compound interactions using DSC, SEM and FTIR and compared to the loadings obtained when a single compound was impregnated. Two synergistic effects were observed and accounted to the plasticizing and cryogenic effect of ketoprofen and carvone that facilitated the diffusion of aspirin and ketoprofen, respectively. Chain mobility and polymer/compound interaction are necessary to the synergy. The preliminary study of in vitro release showed faster ketoprofen and aspirin release from the PLLA double impregnation samples, as a result of their increased free volume.

Supercritical CO2 Impregnation of Alpha-tocopherol in Different Aerogels

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.

Zein/MCM-41 Nanocomposite Film Incorporated with Cinnamon Essential Oil Loaded by Modified Supercritical CO2 Impregnation for Long-Term Antibacterial Packaging.

Antimicrobial medicine and food packages based on bio-based film containing essential oils have attracted great attention worldwide. However, the controlled release of essential oils from these film nanocomposites is still a big challenge. In this study, a long-term antibacterial film nanocomposite composed of zein film and cinnamon essential oil (CEO) loaded MCM-41 silica nanoparticles was prepared. The CEO was loaded into MCM-41 particles via modified supercritical impregnation efficiently with a high drug load (>40 wt%). The morphologies of the prepared nanoparticles and film nanocomposite were characterized by a scanning electron microscope. The release behaviors of CEO under different temperatures, high humidity, continuous illumination and in phosphate buffer solution (PBS) solution were investigated. The results showed that the film nanocomposite had an outstanding release-control effect. The addition of MCM-41 nanoparticles also improved the mechanical properties of zein films. The antibacterial effect of CEO was significantly prolonged by the film nanocomposite; indicating the CEO film nanocomposite fabricated via modified supercritical CO2 impregnation was a potential long-term antibacterial medicine or food package material.