Supercritical Solvent Impregnation Research Articles

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.

Supercritical fluid and cocrystallization technologies for designing antimicrobial food packaging PLA nanocomposite foams loaded with eugenol cocrystals with prolonged release

Searching for effective strategies to modify the release rate of essential oil derivatives is one of the main challenges in designing prolonged-release antimicrobial food packaging materials. Herein, supercritical fluid technology and cocrystallization engineering were used to develop novel eugenol (EU) prolonged-release poly (lactic acid) (PLA) nanocomposite foams. Eugenol-phenazine (EU-PHE) cocrystals, produced by a solvent-free mechanochemical method, were incorporated by supercritical solvent impregnation (SSI) inside PLA nanocomposite foams with different contents of Cloisite30B® (C30B). The effect of the cocrystallization process and C30B content on the EU release kinetics and its relation with their antimicrobial activity by direct contact (anti-attachment) and release in broth culture were studied. The deposition of isolated spherical-shaped micrometric EU-PHE cocrystal particles with 0.8 µm average diameter inside the pores of PLA foams was evidenced by XRD, SEM, DSC, and TGA analyses. The release mechanism of EU and its cocrystal was defined as a quasi-Fickian diffusion process successfully described by the Korsmeyer-Peppas model with release rate constants up to 3.6-fold lower than the release rate constant of pure EU. The impregnated foam samples completely inhibited the attachment of Listeria monocytogenes and Salmonella Enteritidis and provided prolonged antimicrobial activity in broth culture against both food-borne pathogens. This study suggests a new, environmentally friendly method for designing prolonged-release antimicrobial food packaging materials.

Selection of processing parameters for the integrated supercritical CO2 extraction from green tea leaves and extract impregnation onto starch-chitosan based films

The study aimed toward the development of biocompatible and biodegradable polymeric films (starch-chitosan and starch-chitosan-cyclodextrin) with biologically valuable green tea leaf extract using an environmentally friendly integrated process of supercritical fluid extraction (SFE) and supercritical solvent impregnation (SSI). The SFE-SSI process parameters were selected through the initial estimation of the SFE parameters effect (temperatures 35 and 70 °C and the addition of co-solvents ethanol, ethanol/water, and water). The present early-stage work showed that an increase in temperature increased extraction yield (from 0.9 to 4.2%) and caffeine content while it decreased polyphenolic and pigment content as well as antioxidant activity and extract loading onto films (from 7.1 to 0.1%). The addition of co-solvents to sc-CO2 had an adverse effect on extract yield, composition, and loading. The highest recorded total phenolic, flavonoid, chlorophyll A, and caffeine content in extracts were 136.5 mg GE/g, 22.7 mg RE/g, 8.1 mg/g, and 460.0 mg/g, respectively.

Effect of pressure on the supercritical solvent impregnation of pomegranate peel extract into low-density polyethylene films

Effect of pressure on the supercritical solvent impregnation of pomegranate peel extract into low-density polyethylene films

Synergistic Combination of Antimicrobial Peptides and Cationic Polyitaconates in Multifunctional PLA Fibers.

Combining different antimicrobial agents has emerged as a promising strategy to enhance efficacy and address resistance evolution. In this study, we investigated the synergistic antimicrobial effect of a cationic biobased polymer and the antimicrobial peptide (AMP) temporin L, with the goal of developing multifunctional electrospun fibers for potential biomedical applications, particularly in wound dressing. A clickable polymer with pendent alkyne groups was synthesized by using a biobased itaconic acid building block. Subsequently, the polymer was functionalized through click chemistry with thiazolium groups derived from vitamin B1 (PTTIQ), as well as a combination of thiazolium and AMP temporin L, resulting in a conjugate polymer-peptide (PTTIQ-AMP). The individual and combined effects of the cationic PTTIQ, Temporin L, and PTTIQ-AMP were evaluated against Gram-positive and Gram-negative bacteria as well as Candida species. The results demonstrated that most combinations exhibited an indifferent effect, whereas the covalently conjugated PTTIQ-AMP displayed an antagonistic effect, potentially attributed to the aggregation process. Both antimicrobial compounds, PTTIQ and temporin L, were incorporated into poly(lactic acid) electrospun fibers using the supercritical solvent impregnation method. This approach yielded fibers with improved antibacterial performance, as a result of the potent activity exerted by the AMP and the nonleaching nature of the cationic polymer, thereby enhancing long-term effectiveness.

Generation of high-porosity cerium oxide nanoparticles and their functionalization with caryophyllene oxide using supercritical carbon dioxide

Oral diseases affect to millions people worldwide. Metallic nanoparticles are used as novel treatment due to its antimicrobial, antifungal, anti-inflammatory properties. Supercritical anti-solvent process and supercritical solvent impregnation process have been used to create cerium oxide nanoparticles and impregnate them with caryophyllene oxide, an antifungical and anti-microbial compound. High porosity nanoparticles, between 70 and 450 times higher than the raw cerium material were precipitated and impregnated successfully. The antimicrobial activity of impregnated nanoparticles investigated in vitro showed promising results against Staphylococcus aureus.

An ultra-high disulfiram-loaded delivery system achieved by supercritical carbon dioxide technology for copper-enhanced chemotherapy

Disulfiram (DSF) is a conventional alcohol-aversion drug that has recently been explored as a chemotherapeutic agent and has shown excellent anticancer activity in cooperation with Cu2+ ions. However, the existing DSF delivery system has multiple shortcomings, including low drug loading and Cu2+ delivery efficiency, hindering its clinical applicability. Here, we demonstrated a simple but efficient strategy for realizing the controllable loading of hydrophobic DSF into Cu2+-doped mesoporous silica nanoparticles (Cu-MSN) by using supercritical CO2 technology with ultra-high drug loading efficiency. Benefiting from the unique environment of high pressure and solubility, DSF was well dispersed in supercritical CO2 and immersed into the carriers with controllable drug loading. Factorial experiments indicated an optimal condition (55 °C, 250 bar, and 6 h) for the DSF loading up to 30.8 %. In vitro and in vivo experiments demonstrated high Cu2+-enhanced chemotherapeutic efficacy of DSF. In particular, in cooperation with Cu2+ ions in MSN, the formation of complex (CuET) greatly enhanced and prolonged the antitumor effect. Together, our findings indicated that DSF-loaded Cu-MSN prepared using supercritical solvent impregnation (SSI) enhanced the antitumor effect and had potential in anticancer therapy.

Towards a modern approach to traditional use of Helichrysum italicum in dermatological conditions: In vivo testing supercritical extract on artificially irritated skin

Ethnopharmacological relevanceHelichrysum italicum has been widely used in traditional medicine to treat allergies, colds, cough, skin, liver and gallbladder disorders, inflammation, infections, and sleeplessness. Furthermore, it possesses considerable wound healing and skin protective properties, documented by several in vivo studies performed on animals. However, there is a lack of experimental evidence supporting its potential as a topical agent tested by human clinical trials. Aim of the studyThe study aimed to investigate the skin protective activity of cotton gauze and polypropylene non-woven fabric, impregnated with H. italicum extract by the integrated supercritical CO2 extraction-supercritical solvent impregnation process. Materials and methodsThe integrated process of supercritical CO2 extraction of H. italicum and the impregnation of cotton gauze and polypropylene non-woven fabric was performed under 350 bar and 40 °C with and without the addition of ethanol as a cosolvent. Impregnated textile materials were tested in vivo for their bioactivity on irritated human skin. Randomized in vivo studies performed involved assays of both safety and efficacy of the impregnated textiles. The effects were evaluated using the in vivo non-invasive biophysical measurements of the following skin parameters: electrical capacitance, transepidermal water loss, melanin index, erythema index, and skin pH. ResultsBoth cotton gauze and polypropylene non-woven fabric were impregnated with H. italicum extracts under supercritical conditions with considerable values of the impregnation yield (1.97%–4.25%). The addition of ethanol as a cosolvent during the process caused significant changes in the incorporated extracts’ impregnation yield and chemical profile. Both impregnated textile materials were safe, evaluated by their testing on the human skin with no cause of any irritation and redness. However, efficacy studies revealed that polypropylene non-woven fabric impregnated with H. italicum extract with ethanol as a cosolvent, possessed significantly greater potential for skin protection than the other investigated samples. ConclusionsThe present study demonstrated the feasibility of the combined supercritical extraction and impregnation process in developing materials for topical application based on H. italicum extract. The results of in vivo studies performed on human volunteers confirmed the suitability of H. italicum active components to be a part of human skin protective preparations because of their ability to maintain the skin unimpaired. Traditionally claimed applications as a medicinal plant capable of regenerating skin have been scientifically proven, in addition to employing green technology in obtaining the impregnated materials with a broad spectrum of utilization.

Supercritical Fluid Technologies for the Incorporation of Synthetic and Natural Active Compounds into Materials for Drug Formulation and Delivery.

Various active compounds isolated from natural sources exhibit remarkable benefits, making them attractive for pharmaceutical and biomedical applications, such as antioxidant, antimicrobial, and anti-inflammatory activities, which contribute to the treatment of cardiovascular diseases, neurodegenerative disorders, various types of cancer, diabetes, and obesity. However, their major drawbacks are their reactivity, instability, relatively poor water solubility, and consequently low bioavailability. Synthetic drugs often face similar challenges associated with inadequate solubility or burst release in gastrointestinal media, despite being otherwise a safe and effective option for the treatment of numerous diseases. Therefore, drug-eluting pharmaceutical formulations have been of great importance over the years in efforts to improve the bioavailability of active compounds by increasing their solubility and achieving their controlled release in body media. This review highlights the success of the fabrication of micro- and nanoformulations using environmentally friendly supercritical fluid technologies for the processing and incorporation of active compounds. Several novel approaches, namely micronization to produce micro- and nano-sized particles, supercritical drying to produce aerogels, supercritical foaming, and supercritical solvent impregnation, are described in detail, along with the currently available drug delivery data for these formulations.

Supercritical solvent impregnation of sodium valproate nanoparticles on polymers: Characterization and optimization of the operational parameters

To improve the bioavailability and reduce the therapeutic dose and side effects of Sodium valproate (S-VPA), nanoparticles of this drug were loaded on the polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) polymers via the supercritical solvent impregnation (SSI) process. This process was carried out at different pressures (150–250 bar), temperatures (308–328 K), and impregnation times (60–180 min). The Box–Behnken design (BBD) method was applied to study the effect of operational parameters on the S-VPA/PVP and S-VPA/HPMC loadings and optimize the condition. Maximum loadings on both PVP (1.56%) and HPMC (1.5%) were achieved at 250 bar, 318 K, and 180 min. Moreover, the impregnated samples (S-VPA/PVP and S-VPA/HPMC) were investigated by the FTIR, DSC, SEM, DLS, and XRD analysis. The S-VPA nanoparticles with the mean particle size of 27 nm and 128 nm were uniformly impregnated on the PVP and HPMC polymers, respectively. The results confirmed the lower crystallinity of the impregnated S-VPA nanoparticles, leading to their higher solubility and bioavailability. Finally, Enhanced S-VPA solubility was approved by comparing the dissolution rate of the original and the impregnated S-VPA samples in the optimum conditions.

Preparation of ROS-responsive drug-loaded hydrogels applied in wound dressings using supercritical solvent impregnation

Drug-loaded hydrogels with wound environment stimuli-responsive property can significantly promote wound healing and are widely applied in dressings. Two natural polymers, i.e. sodium alginate and sodium hyaluronate, were modified by 3-aminophenylboric acid and then cross-linked with polyvinyl alcohol to prepare ROS responsive hydrogels. Doxycycline hydrochloride was loaded onto hydrogels using supercritical solvent impregnation (SSI) technology, and the effects of immersion time, pressure and temperature on drug loading capacity (DLC) were investigated. DLC firstly increased and then decreased with the elevation of supercritical CO2 pressure, and maximum value was up to 11 mg/g at 15 MPa and 50 °C. In the in vitro drug release study, doxycycline hydrochloride was controllably released from hydrogels for 10 h via the sensitivity of boronate ester bonds to ROS. This work expands the application of SSI in wound dressing, which provides a new approach for the design of composite hydrogel formulations with uniform drug distribution.

Supercritical impregnation of chitosan sponges with 17β-estradiol

Chitosan sponges with open porous structures have great potential as drug delivery matrices for constructing transdermal patches. Supercritical solvent impregnation (SSI) is an advantageous green technique for the inclusion of hydrophobic drugs into porous matrices. In this work SSI of chitosan sponges with 17β-estradiol (E2) using a supercritical scCO2 /ethanol medium under static conditions was investigated. In the SSI study, the influence of such operating parameters as temperature (35 and 65 °C), pressure (15–120 MPa, which corresponds to density of CO2 815–1142 kg m-3.), and a molar fraction of the drug (from 2.3 ×10-3 mol% to 8.9 ×10-3 mol% from CO2 amount) in the reactor on the loading capacity and the efficiency of the uptake was evaluated. It was revealed that hormone loading increased linearly with the initial concentration of E2 and CO2 density in the reactor. The developed processing parameters for SSI made it possible to vary the loading of E2 into the chitosan sponges in a wide range from a few to hundreds of µg per mg of the matrix, which corresponds to the adequate doses range of the hormone used in transdermal delivery. The successful inclusion of E2 into the polymer matrices was proven by UV spectroscopy, powder X-ray diffraction, fluorescence microscopy, and scanning electron microscopy. It was found that SSI method provides a strong micronization and a uniform distribution of E2 crystallites in the sponge volume, which may positively affect the bioavailability of the drug.

Experimental study of ketoconazole impregnation into polyvinyl pyrrolidone and hydroxyl propyl methyl cellulose using supercritical carbon dioxide: Process optimization

This study aims to increase the oral bioavailability of ketoconazole (KET, drug) by incorporating it into water-soluble polymers, using supercritical carbon dioxide (SC-CO2) as the impregnating solvent. For this purpose, loading of KET into poly (vinylpyrrolidone) (PVP) and hydroxy propyl methyl cellulose (HPMC) using supercritical solvent impregnation (SSI) was investigated for the first time. Box-Behnken design (BBD) was used to optimize the impregnation process. Effects of three process parameters, namely pressure (150, 200 and 250 bar), impregnation time (60, 120 and 180 min), and temperature (308, 318 and 328 K) on the loading were studied, leading to a range of 0.33%− 0.98% for KET into PVP and 0.46%− 1.41% for KET into HPMC polymer. Samples were examined using FTIR, DLS, SEM, XRD and DSC analyses. Additionally, the small particle size and the presence of polymers increased the dissolution rate of the drug in aqueous solutions up to 7.3 folds.

Supercritical Extraction of a Natural Pyrethrin-Rich Extract from Chrysanthemum Cinerariifolium Flowers to Be Impregnated into Polypropylene Films Intended for Agriculture Applications

The extensive use of synthetic pesticides and their addition to the field presents significant environmental problems that must be minimized. The use of natural insecticides and their addition using techniques that minimize their impact in the field are widely studied by the current scientific community. In this work an extraction method based on supercritical CO2 to obtain a pyrethrin-rich natural extract from different varieties of chrysanthemum flowers is analyzed. This extract would be used in a supercritical solvent impregnation (SSI) process to produce a commercial polypropylene (PP) film with insecticidal properties to be used in greenhouses. The extract selected for the impregnation process was that obtained from the Atlantis variety at 35 °C and 10 MPa pressure. The amount of insecticide impregnated into the polymer at 55 °C and under two different pressure levels (10 MPa and 40 MPa) have been determined. A batch impregnation method (BM) with 5 h constant impregnation time and low depressurization rates were used to favor the impregnation process. The results demonstrated that this procedure was suitable to produce pyrethrin-loaded PP films that could to be used in greenhouses as a protection against pests, while allowing a more rational and moderate use of other chemical pesticides.

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.

Mass Transfer and Optical Properties of Active PET/PP Food-Grade Films Impregnated with Olive Leaf Extract

A supercritical solvent impregnation (SSI) technique was employed to incorporate, by batch- and semicontinuous-modes, bioactive olive leaf extract (OLE) into a food-grade multilayer polyethylene terephthalate/polypropylene (PET/PP) film for active food packaging applications. The inclusion of OLE in the polymer surfaces significantly modified the colour properties of the film. A correlation of 87.06% between the CIELAB colour parameters and the amount of the OLE impregnated in the film was obtained which suggests that colour determination can be used as a rapid, non-destructive technique to estimate the OLE loading in the impregnated matrices. The UV barrier and water permeability properties of the films were not significantly modified by the incorporation of OLE. The migration of OLE into a 50% (v/v) ethanol food simulant demonstrated faster release of OLE from the PP surface than from the PET surface which may be due to the different interactions between OLE and each polymer.

Utilization of supercritical carbon dioxide for development of antibacterial surgical sutures

Outbreak of surgical infections and bacterial resistance against synthetic antibiotic has prompted research towards development of antibacterial medical devices. For that purpose, absorbable surgical sutures were impregnated with natural compound thymol using an environmentally friendly medium. The supercritical solvent impregnation process was performed at 35 °C and 10 MPa during 1, 2, 3 and 6 h, resulting in thymol loadings of 3.9–5.6%. All tested samples expressed antibacterial activity against E. coli and S. aureus. Release tests in PBS at 37 °C showed that impregnated material released loaded thymol in a gradual manner. While sutures impregnated during 6 h released complete amount of loaded thymol during 6 days, shorter impregnation process resulted in sutures that retained significant thymol amounts (~ 20–40%) after 10 days of release test. The effect of proposed process on final material properties and its application were explained in detail using characterization techniques SEM, FTIR, DSC and DMA.

Supercritical solvent impregnation of alginate wound dressings with mango leaves extract

Supercritical CO2 and a mango leaves extract were used to impregnate calcium-sodium alginate wound dressings. Two methods of impregnation were developed: batch and semi-continuous supercritical impregnation. The influence of parameters such as pressure, temperature and depressurization rate on the impregnation process was studied in terms of the antioxidant capacity of the samples and the impregnation load of polyphenols present in the mango leaves extract. The higher load of mango polyphenols and strong antioxidant capacity were obtained in batch mode at 30 MPa, 35°C and at fast depressurization rate. Semi-continuous mode behaved in a similar way but with lower results according to obtained impregnation percentages in the assayed conditions. The antioxidant capacity of the processed samples was verified by DPPH method, and to confirm the presence of the antioxidant particles and their distribution on the matrix, the processed alginate wound dressings were studied by UPLC-MS and Scanning Electron Microscopy (SEM).

Polymeric Microfiltration Membranes Modification by Supercritical Solvent Impregnation-Potential Application in Open Surgical Wound Ventilation.

This study investigated supercritical solvent impregnation of polyamide microfiltration membranes with carvacrol and the potential application of the modified membranes in ventilation of open surgical wounds. The impregnation process was conducted in batch mode at a temperature of 40 °C under pressures of 10, 15, and 20 MPa for contact times from 1 to 6 h. FTIR was applied to confirm the presence of carvacrol on the membrane surface. In the next step, the impact of the modification on the membrane structure was studied using scanning electron and ion beam microscopy and cross-filtration tests. Further, the release of carvacrol in carbon dioxide was determined, and finally, an open thoracic cavity model was applied to evaluate the efficiency of carvacrol-loaded membranes in contamination prevention. Carvacrol loadings of up to 43 wt.% were obtained under the selected operating conditions. The swelling effect was detectable. However, its impact on membrane functionality was minor. An average of 18.3 µg of carvacrol was released from membranes per liter of carbon dioxide for the flow of interest. Membranes with 30–34 wt.% carvacrol were efficient in the open thoracic cavity model applied, reducing the contamination levels by 27% compared to insufflation with standard membranes.

Potential Use of Annona Genus Plants Leaf Extracts to Produce Bioactive Transdermal Patches by Supercritical Solvent Impregnation.

The objective of the present work was to develop a bioactive transdermal patch functionalized with Annona leaf extracts (ALE) by means of supercritical impregnation technique. The potential of six different Annona leaf extracts (ALE) obtained with the enhanced solvent system formed by carbon dioxide + ethanol/acetone was evaluated taking into account the antioxidant activity, total phenol composition and global extraction yields. For the impregnation of ALE, two drug supporting systems were tested: hydrocolloid sodium carboxymethyl cellulose (NaCMC) and polyester dressings (PD). The effect of the impregnation conditions, including pressure (P), temperature (T), percent of co-solvent (ethanol) and ALE/polymer mass ratio, was determined with regard to the loading and the functional activity of the impregnated samples. The optimal impregnation conditions of ALE were established at 55 °C and 300 bar which led to obtained transdermal patches with antioxidant and antimicrobial capacity. In order to understand the behavior of the process, the homogeneity of the samples in the vessels was also evaluated. The best results were obtained at higher proportions of co-solvent in the system.