Low drug bioavailability, which is mostly a result of poor aqueous drug solubilities and of inadequate drug dissolution rates, is one of the most significant challenges that pharmaceutical companies ...are currently facing, since this may limit the therapeutic efficacy of marketed drugs, or even result in the discard of potential highly effective drug candidates during developmental stages. Two of the main approaches that have been implemented in recent years to overcome poor drug solubility/dissolution issues have frequently involved drug particle size reduction (i.e., micronization/nanonization) and/or the modification of some of the physicochemical and structural properties of poorly water soluble drugs. A large number of particle engineering methodologies have been developed, tested, and applied in the synthesis and control of particle size/particle-size distributions, crystallinities, and polymorphic purities of drug micro- and nano-particles/crystals. In recent years pharmaceutical processing using supercritical fluids (SCF), in general, and supercritical carbon dioxide (scCO2), in particular, have attracted a great attention from the pharmaceutical industry. This is mostly due to the several well-known advantageous technical features of these processes, as well as to other increasingly important subjects for the pharmaceutical industry, namely their “green”, sustainable, safe and “environmentally-friendly” intrinsic characteristics.
In this work, it is presented a comprehensive state-of-the-art review on scCO2-based processes focused on the formation and on the control of the physicochemical, structural and morphological properties of amorphous/crystalline pure drug nanoparticles. It is presented and discussed the most relevant scCO2, scCO2-based fluids and drug physicochemical properties that are pertinent for the development of successful pharmaceutical products, namely those that are critical in the selection of an adequate scCO2-based method to produce pure drug nanoparticles/nanocrystals. scCO2-based nanoparticle formation methodologies are classified in three main families, and in terms of the most important role played by scCO2 in particle formation processes: as a solvent; as an antisolvent or a co-antisolvent; and as a “high mobility” additive (a solute, a co-solute, or a co-solvent). Specific particle formation methods belonging to each one of these families are presented, discussed and compared. Some selected amorphous/crystalline drug nanoparticles that were prepared by these methods are compiled and presented, namely those studied in the last 10–15 years. A special emphasis is given to the formation of drug cocrystals. It is also discussed the fundamental knowledge and the main mechanisms in which the scCO2-based particle formation methods rely on, as well as the current status and urgent needs in terms of reliable experimental data and of robust modeling approaches. Other addressed and discussed topics include the currently available and the most adequate physicochemical, morphological and biological characterization methods required for pure drug nanoparticles/nanocrystals, some of the current nanometrology and regulatory issues associated to the use of these methods, as well as some scale-up, post-processing and pharmaceutical regulatory subjects related to the industrial implementation of these scCO2-based processes. Finally, it is also discussed the current status of these techniques, as well as their future major perspectives and opportunities for industrial implementation in the upcoming years.
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This work reports the development of porous poly (ε-caprolactone) (PCL)-based intraocular implants, prepared by green supercritical carbon dioxide (scCO2) foaming/mixing method (SFM), ...to produce implants that degrade faster than typical slow-degrading PCL-based implants. The higher porosities and surface areas of these implants led to faster degradation rates at in vitro accelerated alkaline conditions than low porosity/surface area implants prepared by hot melting processing. These porous implants also presented distinct (faster) release rates of a test-drug (dexamethasone). Additionally, these porous devices did not cause cell death and did not reduce the number of neurons, indicating that are not toxic to retinal cells. We further explored the impact of PCL-based implant to the retina by in vivo evaluation and histological analysis. Implants were surgically inserted in the vitreous of Wistar rats, and their presence did not change the function, structure and anatomy of the retina. These devices demonstrated a good intraocular tolerance, further confirming their viability for prolonged drug delivery applications. Further comprehensive studies based on this promising preliminary assessment and proof-of-concept could enable its future translation to clinical protective strategies for retinal diseases.
The olive mill wastewaters obtained from two different processes, press extraction olive mill wastewater (POMW) from Portugal and two-phase system olive mill wastewater (2POMW) from Spain, were ...treated to recover phenolic compounds and water sequentially, by the integration of liquid-liquid extraction with Fenton’s processes. From the recovered fractions, squalene, oleic acid, tyrosol, syringic acid, and p-coumaric acid were identified, and oleic acid appears in a higher concentration for 2POMW wastewater for all used solvents compared to POMW samples. Recovered fractions presented higher antioxidant activity, but remained antioxidants were found in the residual water. The wastewaters coming from a two-phase extraction method (2POMW) present higher phytotoxicity according to germination index, but the application of Fenton’s process was able to improve the water quality to be re-used since an increase on the water biodegradability (BOD5/COD) and toxicity reduction were achieved.
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Hydrogels are extensively used in the biomedical field, as drug delivery systems, wound dressings, contact lenses or as scaffolds for tissue engineering. Due to their polymeric nature ...and the presence of high amounts of water in their structure, hydrogels generally present high sensitivity to terminal sterilization. The establishment of an efficient sterilization protocol that does not compromise the functional properties of the hydrogels is one of the challenges faced by researchers when developing a hydrogel for a specific application. Yet, until very recently this aspect was largely ignored in the literature. The present paper reviews the state of literature concerning hydrogels sterilization, compiling the main findings. Conventional terminal sterilization methods (heat sterilization, radiation sterilization, and gas sterilization) as well as emerging sterilization techniques (ozone, supercritical carbon dioxide) are covered. Considerations about aseptic processing are also included. Additionally, and as a framework, hydrogels’ polymeric materials, types of networks, and main biomedical applications are summarily described.
The aim of this work was to develop an innovative supercritical fluid (SCF)-assisted molecular imprinting method to endow commercial soft contact lenses (SCLs) with the ability to load specific drugs ...and to control their release. This approach seeks to overcome the limitation of the common loading of preformed SCLs by immersion in concentrated drug solutions (only valid for highly water soluble drugs) and of the molecular imprinting methods that require choice of the drug before polymerization and thus to create drug-tailored networks. In particular, we focused on improving the flurbiprofen load/release capacity of daily wear Hilafilcon B commercial SCLs by the use of sequential SCF flurbiprofen impregnation and extraction steps. Supercritical carbon dioxide (scCO₂) impregnation assays were performed at 12.0MPa and 40°C, while scCO₂ extractions were performed at 20.0MPa and 40°C. Conventional flurbiprofen sorption and drug removal experiments in aqueous solutions were carried out for comparison purposes. SCF-processed SCLs showed a recognition ability and a higher affinity for flurbiprofen in aqueous solution than for the structurally related ibuprofen and dexamethasone, which suggests the creation of molecularly imprinted cavities driven by both physical (swelling/plasticization) and chemical (carbonyl groups in the network with the C–F group in the drug) interactions. Processing with scCO₂ did not alter some of the critical functional properties of SCLs (glass transition temperature, transmittance, oxygen permeability, contact angle), enabled the control of drug loaded/released amounts (by the application of several consecutive processing cycles) and permitted the preparation of hydrophobic drug-based therapeutic SCLs in much shorter process times than those using conventional aqueous-based molecular imprinting methods.
Food packaging trends have been changing in the last years, mainly due to consumer concerns about plastic pollution and agrifood waste. Recent advances in the development of edible films and coatings ...are discussed. These systems can be much more than packaging, with additional functions such as antioxidant, antimicrobial, and nutritional properties, among others. Challenges in industrial processes and/or in some films’ properties are addressed from the authors’ point of view. The use of agrifood residues in these packaging systems is included as a promising strategy that promotes sustainability and circular economy. The authors consider that more research and actions are needed to achieve the best packaging material for each food product with reduced production costs.
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•The food packaging sector has changed from conventional to sustainable systems.•Edible films and coatings appear as a new trend with advantages and challenges.•Use of food residues is promising in the packaging sector.•More research/actions are needed to have packaging based on residues in the market.
The preparation of alginate films with suitable properties requires a two-step contact with reticulating agents: initially a weakly structured pre-film is formatted which is further crosslinked in a ...second stage by immersion in a more concentrated solution. The present work evaluated the effects of a combined crosslinking procedure using calcium and barium ions on the physical and morphological properties of alginate-based films containing natamycin as antimicrobial agent. The release behavior of natamycin in water was evaluated as well as the antimicrobial activity against four target microorganisms, which are common cheese product contaminants. Films attributes were affected by the type of ion used in the second stage while the natamycin release rate and the antimicrobial activity were influenced by the ion used in the first stage. Films crosslinked with Ba2+ in the first and Ca2+ in the second stage (Ba–Ca films) exhibited physical properties very similar to films crosslinked with calcium in both stages. Release kinetics of natamycin in water fitted well to Fick's second law diffusional model, with effective diffusivity values ranging from 0.40 × 10−11 to 1.74 × 10−11 cm2/s. Ba–Ca films presented the lowest natamycin diffusion coefficient and the smallest inhibition zone diameter against the four microorganisms tested.
•Alginate films were crosslinked with Ca2+ and/or Ba2+ ions by a two-stage method.•Films crosslinked with Ba2+ in the second stage showed unsuitable barrier properties.•The type of crosslinking ion strongly affects the natamycin diffusion process.•In vitro antimicrobial effectiveness of the films containing natamycin was validated.•Films feature potential requirements to act as antimicrobial packaging for cheeses.
The efficiency of photodynamic therapy is often limited by the scarcity of oxygen at the target site. To address this problem, this work proposes the development of a new nanosystem for antimicrobial ...photodynamic therapy applications (aPDT) where the natural-origin photosensitizer curcumin (CUR) is immersed in an oxygen-rich environment. Inspired by the perfluorocarbon-based photosensitizer/O
nanocarriers reported in the literature, we developed a new type of silica nanocapsule containing curcumin dissolved in three hydrophobic ionic liquids (ILs) with high oxygen dissolving capacities. The nanocapsules (CUR-IL@ncSi), prepared by an original oil-in-water microemulsion/sol-gel method, had a high IL content and exhibited clear capacities to dissolve and release significant amounts of oxygen, as demonstrated by deoxygenation/oxygenation studies. The ability of CUR-IL solutions and of CUR-IL@ncSi to generate singlet oxygen (
O
) upon irradiation was confirmed by the detection of
O
phosphorescence at 1275 nm. Furthermore, the enhanced capacities of oxygenated CUR-IL@ncSi suspensions to generate
O
upon irradiation with blue light were confirmed by an indirect spectrophotometric method. Finally, preliminary microbiological tests using CUR-IL@ncSi incorporated into gelatin films showed the occurrence of antimicrobial effects due to photodynamic inactivation, with their relative efficiencies depending on the specific IL in which curcumin was dissolved. Considering these results, CUR-IL@ncSi has the potential to be used in the future to develop biomedical products with enhanced oxygenation and aPDT capacities.
The root-knot nematode (RKN)
presents a threat to the production of several important crops. This nematode species was added to the European Plant Protection Organization Alert list in 2017. The ...scarce availability of efficient nematicides to control RKN and the phasing out of nematicides from the market have intensified the search for alternatives, such as phytochemicals with bionematicidal properties. The nematicidal activity of 1,4-naphthoquinone (1,4-NTQ) against
has been demonstrated; however, knowledge of the potential mode(s) of action of this compound is still scarce. In this study, the transcriptome profile of
second-stage juveniles (J2), the infective stage, in response to 1,4-NTQ exposure was determined by RNA-seq to identify genes and pathways that might be involved in 1,4-NTQ's mode(s) of action. Control treatments, consisting of nematodes exposed to Tween
80 (1,4-NTQ solvent) and to water, were included in the analysis. A large set of differentially expressed genes (DEGs) was found among the three tested conditions, and a high number of downregulated genes were found between 1,4-NTQ treatment and water control, reflecting the inhibitory effect of this compound on
, with a great impact on processes related to translation (ribosome pathway). Several other nematode gene networks and metabolic pathways affected by 1,4-NTQ were also identified, clarifying the possible mode of action of this promising bionematicide.
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