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Every year, grapevine pruning produces huge amounts of residue, 90% of which are from vine shoots. These are a rich source of natural antioxidants, mostly phenolic compounds, which, when properly extracted, can give rise to added-value products. However, their lack of solubility in aqueous media and high susceptibility to thermal and oxidative degradation highly limit their bioavailability. Encapsulation in suitable carriers may have a positive impact on their bioavailability and bioactivity. Previous data on vine-shoot extraction have identified gallic acid (GA) and resveratrol (RSV) as the main phenolic compounds. In this work, model dry powder formulations (DPFs) of GA and RSV using hydroxypropyl cellulose (HPC) as carriers were developed using Supercritical CO2-Assisted Spray Drying (SASD). A 32 full factorial Design of Experiments investigated the solid and ethanol contents to ascertain process yield, particle size, span, and encapsulation efficiency. Amorphous powder yields above 60%, and encapsulation efficiencies up to 100% were achieved, representing excellent performances. SASD has proven to be an efficient encapsulation technique for these phenolic compounds, preserving their antioxidation potential after three months in storage with average EC50 values of 30.6 µg/mL for GA-DPFs and 149.4 µg/mL for RSV-DPF as assessed by the scavenging capacity of the DPPH radical.
Assuntos
Dióxido de Carbono , Secagem por Atomização , Dessecação , Fenóis/química , Extratos Vegetais/químicaRESUMO
Drug delivery systems (DDS) often comprise biopharmaceuticals in aqueous form, making them susceptible to physical and chemical degradation, and therefore requiring low temperature storage in cold supply and distribution chains. Freeze-drying, spray-drying, and spray-freeze-drying are some of the techniques used to convert biopharmaceuticals-loaded DDS from aqueous to solid dosage forms. However, the risk exists that shear and heat stress during processing may provoke DDS damage and efficacy loss. Supercritical fluids (SCF), specifically, supercritical carbon dioxide (scCO2), is a sustainable alternative to common techniques. Due to its moderately critical and tunable properties and thermodynamic behavior, scCO2 has aroused scientific and industrial interest. Therefore, this article reviews scCO2-based techniques used over the year in the production of solid biopharmaceutical dosage forms. Looking particularly at the use of scCO2 in each of its potential roles-as a solvent, co-solvent, anti-solvent, or co-solute. It ends with a comparison between the compound's stability using supercritical CO2-assisted atomization/spray-drying and conventional drying.
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Produtos Biológicos/química , Química Farmacêutica , Sistemas de Liberação de Medicamentos , Dióxido de Carbono/química , LiofilizaçãoRESUMO
Water is one of the most valuable resources today and its purity is crucial to health and society well-being. The access to safe drinking water is decreasing in the world, which can have a huge socio-economic impact especially in developing countries, more prone to water-associated diseases. The goal of this work was to develop an innovative, fast, and cost-effective 3D material capable of decontaminating water. We have used an eco-friendly strategy, combining plasma surface activation and supercritical fluid technology to produce, for the first time, a 2-oxazoline-grafted 3D surface with broad-spectrum contact-active antimicrobial properties. Oligo(2-methyl-2-oxazoline) quaternized with N,N-dimethyldodecylamine and grafted to a chitosan (CHT) scaffold (CHT-OMetOx-DDA) efficiently and quickly (<3 min) killed >99.999% of Staphylococcus aureus and Escherichia coli cells upon direct contact and avoided bacterial adhesion to the materials surface, which is important for the prevention of biofilm formation. As a proof of concept, CHT-OMetOx-DDA scaffold was demonstrated to be suitable for water purification efficiently killing the microorganisms present in different water samples within minutes of contact and without leaching to the water. Additionally, we report for the first time a new method to clearly distinguish two mechanisms of action of bioactive surfaces: contact-active and releasing systems.
Assuntos
Anti-Infecciosos/farmacologia , Quitosana/química , Dimetilaminas/química , Desinfetantes/farmacologia , Oxazóis/química , Purificação da Água/métodos , Anti-Infecciosos/síntese química , Desinfetantes/síntese química , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Água Doce/microbiologia , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Propriedades de Superfície , Fatores de TempoRESUMO
The integrated use of supercritical carbon dioxide (scCO(2)) and micro- and nanotechnologies has enabled new sustainable strategies for the manufacturing of new medications. 'Green' scCO(2)-based methodologies are well suited to improve either the synthesis or materials processing leading to the assembly of three-dimensional multifunctional constructs. By using scCO(2) either as C1 feedstock or as solvent, simple, economic, efficient and clean routes can be designed to synthesize materials with unique properties such as polyurea dendrimers and oxazoline-based polymers/oligomers. These new biocompatible, biodegradable and water-soluble polymeric materials can be engineered into multifunctional constructs with antimicrobial activity, targeting moieties, labelling units and/or efficiently loaded with therapeutics. This mini-review highlights the particular features exhibited by these materials resulting directly from the followed supercritical routes.
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Affinity chromatography is one of the most common techniques employed at the industrial-scale for antibody purification. In particular, the purification of human immunoglobulin G (hIgG) has gained relevance with the immobilization of its natural binding counterpart-Staphylococcus aureus Protein A (SpA) or with the recent development of biomimetic affinity ligands, namely triazine-based ligands. These ligands have been developed in order to overcome economic and leaching issues associated to SpA. The most recent triazine-based ligand-TPN-BM, came up as an analogue of 2-(3-amino-phenol)-6-(4-amino-1-naphthol)-4-chloro-sym-triazine ligand also known as ligand 22/8 with improved physico-chemical properties and a greener synthetic route. This work intends to evaluate the potential of TPN-BM as an alternative affinity ligand towards antibody recognition and binding, namely IgG, at an atomic level, since it has already been tested, after immobilization onto chitosan-based monoliths and demonstrated interesting affinity behaviour for this purpose. Herein, combining automated molecular docking and molecular dynamics simulations it was predicted that TPN-BM has high propensity to bind IgG through the same binding site found in the crystallographic structure of SpA_IgG complex, as well as theoretically predicted for ligand 22/8_IgG complex. Furthermore, it was found that TPN-BM established preferential interactions with aromatic residues at the Fab domain (Trp 50, Tyr 53, Tyr 98 and Trp 100), while in the Fc domain the main interactions are based on hydrogen bonds with pH sensitive residues at operational regime for binding and elution like histidines (His 460, His 464, His 466). Moreover, the pH dependence of TPN-BM_IgG complex formation was more evident for the Fc domain, where at pH 3 the protonation state and consequently the charge alteration of histidine residues located at the IgG binding site induced ligand detachment which explains the optimal elution condition at this pH observed experimentally.
Assuntos
Anticorpos/isolamento & purificação , Imunoglobulina G/química , Proteína Estafilocócica A/química , Anticorpos/química , Anticorpos/imunologia , Sítios de Ligação , Biomimética , Cromatografia de Afinidade , Humanos , Ligação de Hidrogênio , Imunoglobulina G/imunologia , Ligantes , Simulação de Dinâmica Molecular , Ligação Proteica , Staphylococcus aureus/química , Staphylococcus aureus/imunologiaRESUMO
This paper presents a sustainable strategy for improving the capture of antibodies by affinity chromatography. A novel biomimetic ligand (4-((4-chloro-6-(3-hydroxyphenoxy)-1,3,5-triazin-2-yl)oxy)naphthalen-1-ol) (TPN-BM) was synthesized using a greener and simple protocol to overcome solubility limitations associated with ligand 22/8, known as artificial protein A. Furthermore, its subsequent immobilization on chitosan-based monoliths induced by plasma surface activation allowed the design of a fast and efficient chromatographic platform for immunoglobulin G (IgG) purification. The TPN-BM functionalized monoliths exhibited high-binding capacity (160 ± 10 mg IgG per gram of support), and a selective capture of monoclonal antibodies directly from mammalian crude extracts in 85 ± 5% yield and 98% of purity. The synthesis of ligand TPN-BM and the routes followed for monoliths preparation and functionalization were inspired in the green chemistry principles allowing the reduction of processing time, solvents and purification steps involved, turning the integrated system attractive from an economical and chemical point of view.
Assuntos
Anticorpos/isolamento & purificação , Biomimética/métodos , Animais , Anticorpos/química , Anticorpos Monoclonais/química , Anticorpos Monoclonais/isolamento & purificação , Cromatografia de Afinidade , Imunoglobulina G/química , Imunoglobulina G/isolamento & purificaçãoRESUMO
The production, characterization and anti-biofouling activity of 3D porous scaffolds combining different blends of chitosan and oxazoline-based antimicrobial oligomers is reported. The incorporation of ammonium quaternized oligo(2-oxazoline)s into the composition of the scaffold enhances the stability of the chitosan scaffold under physiological conditions as well as its ability to repel protein adsorption. The blended scaffolds showed mean pore sizes in the range of 18-32 µm, a good pore interconnectivity and high porosity, as well as a large surface area, ultimate key features for anti-biofouling applications. Bovine serum albumin (BSA) adhesion profiles showed that the composition of the scaffolds plays a critical role in the chitosan-oligooxazoline system. Oligobisoxazoline-enriched scaffolds (20% w/w, CB8020) decreased protein adsorption (BSA) by up to 70%. Moreover, 1 mg of CB8020 was able to kill 99.9% of Escherichia coli cells upon contact, demonstrating its potential as promising material for production of tailored non-fouling 3D structures to be used in the construction of novel devices with applications in the biomedical field and water treatment processes.
Assuntos
Antibacterianos/farmacologia , Biofilmes , Incrustação Biológica/prevenção & controle , Quitosana/química , Animais , Antibacterianos/síntese química , Antibacterianos/química , Aderência Bacteriana , Bovinos , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Liofilização , Viabilidade Microbiana , Conformação Molecular , Oxazóis/química , Oxazóis/farmacologia , Porosidade , Soroalbumina Bovina/química , Alicerces Teciduais/químicaRESUMO
The layer-by-layer (LbL) assembly of polyelectrolyte pairs on temperature and pH-sensitive cross-linked poly(N-isopropylacrylamide)-co-(methacrylic acid), poly(NIPAAm-co-MAA), microgels enabled a fine-tuning of the gel swelling and responsive behavior according to the mobility of the assembled polyelectrolyte (PE) pair and the composition of the outermost layer. Microbeads with well-defined morphology were initially prepared by synthesis in supercritical carbon dioxide. Upon LbL assembly of polyelectrolytes, interactions between the multilayers and the soft porous microgel led to differences in swelling and thermoresponsive behavior. For the weak PE pairs, namely poly(L-lysine)/poly(L-glutamic acid) and poly(allylamine hydrochloride)/poly(acrylic acid), polycation-terminated microgels were less swollen and more thermoresponsive than native microgel, whereas polyanion-terminated microgels were more swollen and not significantly responsive to temperature, in a quasi-reversible process with consecutive PE assembly. For the strong PE pair, poly(diallyldimethylammonium chloride)/poly(sodium styrene sulfonate), the differences among polycation and polyanion-terminated microgels are not sustained after the first PE bilayer due to extensive ionic cross-linking between the polyelectrolytes. The tendencies across the explored systems became less noteworthy in solutions with larger ionic strength due to overall charge shielding of the polyelectrolytes and microgel. ATR FT-IR studies correlated the swelling and responsive behavior after LbL assembly on the microgels with the extent of H-bonding and alternating charge distribution within the gel. Thus, the proposed LbL strategy may be a simple and flexible way to engineer smart microgels in terms of size, surface chemistry, overall charge and permeability.
Assuntos
Acrilamidas/química , Ácidos Polimetacrílicos/química , Dióxido de Carbono/química , Géis , Concentração de Íons de Hidrogênio , Fenômenos Mecânicos , Propriedades de Superfície , TemperaturaRESUMO
The biopharmaceuticals market is constantly growing. Despite their advantages over the conventional drugs, biopharmaceuticals have short biological half-lifes, which can be increased using liposomes. However, the common bulk methods to produce biopharmaceuticals-loaded liposomes result in lost of encapsulation efficiency (E.E.), resulting in an expensive process. Herein, the encapsulation of a therapeutic enzyme in liposomes is proposed, using a glass-capillary microfluidic technique. Cu,Zn- Superoxide dismutase (SOD) is successfully encapsulated into liposomes (SOD@Liposomes). SOD@Liposomes with a mean size of 135 ± 41 nm, a polydispersity index of 0.13 ± 0.01, an E.E. of 59 ± 6 % and an enzyme activity of 82 ± 3 % are obtained. in vivo experiments show, through an ear edema model, that SOD@Liposomes administered by the intravenous route enable an edema inhibition of 65 % ± 8 %, over the 20 % ± 13 % of SOD in its free form. The histopathological analyses show a higher inflammatory cell accumulation on the ear treated with SOD in its free form, than treated with SOD@Liposomes. Overall, this work highlights the potential of microfluidics for the production of enzyme-loaded liposomes with high encapsulation efficiency, with the intrinsic advantages of the low time-consuming and easily upscaling microfluidic assembly method.
Assuntos
Lipossomos , Microfluídica , Edema , Humanos , Injeções Intravenosas , Superóxido DismutaseRESUMO
Small interfering RNA (siRNA) therapy has significant potential for the treatment of myriad diseases, including cancer. While intravenous routes of delivery have been found to be effective for efficient targeting to the liver, achieving high accumulations selectively in other organs, including lung tissues, can be a challenge. We demonstrate the rational design and engineering of a layer-by-layer (LbL) nanoparticle-containing aerosol that is able to achieve efficient, multistage delivery of siRNA in vitro. For the purpose, LbL nanoparticles were, for the first time, encapsulated in composite porous micro scale particles using a supercritical CO2-assisted spray drying (SASD) apparatus using chitosan as an excipient. Such particles exhibited aerodynamic properties highly favorable for pulmonary administration, and effective silencing of mutant KRAS in lung cancer cells derived from tumors of a non-small cell lung cancer (NSCLC) autochthonous model. Furthermore, efficient alveolar accumulation following inhalation in healthy mice was also observed, corroborating in vitro aerodynamic results, and opening new perspectives for further studies of effective lung therapies These results show that multistage aerosols assembled by supercritical CO2-assisted spray drying can enable efficient RNA interference therapy of pulmonary diseases including lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas , Administração por Inalação , Aerossóis , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Excipientes , Pulmão , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Camundongos , Interferência de RNA , RNA Interferente PequenoRESUMO
Lopinavir (LPV) is currently used in combination with ritonavir for the clinical management of HIV infections due to its limited oral bioavailability. Herein, we report the application of an in silico method to study cyclodextrin (CyD) host-guest molecular interaction with LPV for the rational selection of the best CyD for developing a CyD based LPV delivery system. The predicted CyD, a (2-hydroxy)propyl-gamma derivative with high degree of substitution (HP17-γ-CyD) was synthesized and comparatively evaluated with γ-CyD and the commercially available HP-γ-CyD. All complexes were prepared by supercritical assisted spray drying (SASD) and co-evaporation (CoEva) at molar ratios (1:1 and 1:2); and afterwards fully characterized. Results indicate a higher LPV amorphization and solubilization ability of HP17-γ-CyD. The SASD processing technology also enhanced LPV solubilization and release from complexes. The application of in silico methodologies is a feasible approach for the rational and/or deductive development of CyD drug delivery systems.
Assuntos
Antirretrovirais/química , Lopinavir/química , gama-Ciclodextrinas/química , Simulação por Computador , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , SolubilidadeRESUMO
Here, a continuous two-step glass-capillary microfluidic technique to produce a multistage oral delivery system is reported. Insulin is successfully encapsulated into liposomes, which are coated with chitosan to improve their mucoadhesion. The encapsulation in an enteric polymer offers protection from the harsh gastric conditions. Insulin permeability is enhanced across an intestinal monolayer.
Assuntos
Quitosana/administração & dosagem , Sistemas de Liberação de Medicamentos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Nanopartículas/administração & dosagem , Administração Oral , Células CACO-2 , Quitosana/química , Liberação Controlada de Fármacos , Células HT29 , Humanos , Concentração de Íons de Hidrogênio , Hipoglicemiantes/química , Insulina/química , Lipossomos , Microfluídica , Nanopartículas/químicaRESUMO
To accomplish a rapid wound healing it is necessary to develop an asymmetric membrane with interconnected pores consisting of a top layer that prevents rapid dehydration of the wound and bacteria penetration and a sub-layer with high absorption capacity and bactericidal properties. Polycaprolactone (PCL)/polyvinyl acetate (PVAc) asymmetric membranes loaded with the bactericidal monoterpene carvacrol (CRV) were synthesized and characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. Mechanical properties in dry and wet conditions and fluid handling behavior were also assessed. In addition, biological studies regarding their bactericidal effects, cytocompatibility and wound closure properties were also developed. Loading efficiencies of 40-50% were achieved in the prepared samples and 85-100% of the loaded CRV was released in simulated wound pH evolution medium. The significant inhibition of Gram negative (Escherichia coli S17) and Gram positive (Staphylococcus aureus ATCC 25923) bacteria growth clearly showed the suitability of the fabricated membranes for wound healing applications. Furthermore, cytocompatibility of the loaded membranes was demonstrated both in 2D and 3D human dermal fibroblast cultures, as well as cell migration was not impaired by released carvacrol from the membranes. These results highlight the potential of these polymeric electrospun membranes for wound healing.
Assuntos
Antibacterianos/farmacologia , Bandagens , Membranas Artificiais , Cicatrização , Antibacterianos/química , Antibacterianos/farmacocinética , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Cimenos/química , Cimenos/farmacocinética , Módulo de Elasticidade , Escherichia coli/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Teste de Materiais , Poliésteres/química , Polivinil/química , Staphylococcus aureus/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológicoRESUMO
POxylated polyurea dendrimer (PUREG4OOx48)-based nanoparticles were loaded with paclitaxel (PTX) and doxorubicin (DOX) and micronized with chitosan (CHT) by using supercritical CO2-assisted spray drying (SASD). Respirable, biocompatible, and biodegradable dry powder formulations (DPFs) were produced to effectively transport and deliver the chemotherapeutics with a controlled rate to the deep lung. Inâ vitro studies performed with the use of the lung adenocarcinoma cell line showed that DOX@PUREG4OOx48 nanoparticles were much more cytotoxic than the free drug. Additionally, the DPFs did not show higher cytotoxicity than the respective nanoparticles, and DOX-DPFs showed a higher chemotherapeutic effect than PTX formulations in adenocarcinoma cells.
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The carbon and fluorine chemical shifts of mixtures of carbon dioxide and Krytox, a carboxylic acid end-capped perfluorinated polyether used as stabilizer for the dispersion polymerization of methyl methacrylate, have been studied using high-pressure, high-resolution nuclear magnetic resonance. 13C and 19F spectra were measured in the density region between 0.54 and 0.73 g.cm(-3) at 334 K for different solutions of Krytox in scCO2 (0.22, 1.13 and 1.72 w/w %). An in-house developed high-pressure apparatus with the capability to change in situ the sample composition was used for this purpose using a 10 mm polyether ketone NMR tube. The nature of CO2-Krytox interaction was assessed both by comparing the CO2 deltaC variation of neat CO2 with that of mixtures with increasing surfactant composition and by the analysis of Krytox 19F corrected chemical shifts in terms of medium magnetic susceptibility. Ab initio calculations, at the second-order Møller-Plesset level of theory to include the effects of electron correlation, were performed to access and compare the nature of the interactions between CO2 and perfluorinated and nonfluorinated analogue model molecules. Both experimental 13C and 19F HP-NMR results and molecular modeling studies support a F...CO2 site-specific Lewis acid-Lewis base interaction model. A positive entropic variation for the formation of CO2-fluorinated solute complex is advanced as an explanation for the higher solubility of perfluorinated molecules when compared to the nonfluorinated analogues.
Assuntos
Materiais Biocompatíveis , Dendrímeros , Concentração de Íons de Hidrogênio , Polímeros/química , Células Cultivadas , Humanos , Espectroscopia de Ressonância Magnética , Microscopia Confocal , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
During wound healing, an early inflammation can cause an increase of the wound size and the healing process can be considerably belated if a disproportionate inflammatory response occurs. (S)-ibuprofen (IBP), a non-steroidal anti-inflammatory agent, has been used for muscle healing and to treat venous leg ulcers, but its effect in skin wound healing has not been thoroughly studied thus far. Herein, IBP-ß-cyclodextrins carriers were designed to customise the release profile of IBP from poly(vinyl alcohol)/chitosan (PVA/CS) dressings in order to promote a faster skin regeneration. The dressings were produced using supercritical carbon dioxide (scCO2)-assisted technique. In vitro IBP release studies showed that ß-cyclodextrins allowed a controlled drug release from the hydrogels which is crucial for their application in wound management. Moreover, the in vivo assays revealed that the presence of PVA/CS membranes containing IBP-ß-cyclodextrins carriers avoided scab formation and an excessive inflammation, enabling an earlier skin healing.
Assuntos
Quitosana/química , Ibuprofeno/química , Pele/lesões , Cicatrização , Animais , Bandagens/normas , Células Cultivadas , Feminino , Humanos , Álcool de Polivinil/química , Ratos , Ratos WistarRESUMO
Lung cancer is one of the leading causes of death worldwide. Therefore, it is of extreme importance to develop new systems that can deliver anticancer drugs into the site of action when initiating a treatment. Recently, the use of nanotechnology and particle engineering has enabled the development of new drug delivery platforms for pulmonary delivery. In this work, POXylated strawberry-like gold-coated magnetite nanocomposites and ibuprofen (IBP) were encapsulated into a chitosan matrix using Supercritical Assisted Spray Drying (SASD). The dry powder formulations showed adequate morphology and aerodynamic performances (fine particle fraction 48%-55% and aerodynamic diameter of 2.6-2.8 µm) for deep lung deposition through the pulmonary route. Moreover, the release kinetics of IBP was also investigated showing a faster release of the drug at pH 6.8, the pH of lung cancer. POXylated strawberry-like gold-coated magnetite nanocomposites proved to have suitable sizes for cellular internalization and their fluorescent capabilities enable their future use in in vitro cell based assays. As a proof-of-concept, the reported results show that these nano-in-micro formulations could be potential drug vehicles for pulmonary administration.
RESUMO
Functionalized gold nanoparticles (AuNPs) have been widely investigated as promising multifunctional nanosystems for the theragnosis of lung cancer, the most common and prominent cause of cancer death worldwide. Nevertheless, nanoparticles are not in appropriate sizes for an accurate deep lung delivery and the lack of locally and effective delivery of therapeutic biomolecules to the deep lungs is, in fact, the major cause of low therapeutic outcome. Herein we incorporate, for the first time, AuNPs into respirable microparticles. AuNPs were functionalized with biocompatible oligo(2-oxazoline)-based optically stable fluorescent coatings, and conjugated with a laminin peptide (YIGSR) for targeted lung cancer delivery. These POxylated AuNPs were then incorporated into a chitosan matrix by a clean process, supercritical CO2-assisted spray drying (SASD), yielding nano-in-micro clean ultrafine dry powder formulations. The engineered formulations present the adequate morphology and flowability to reach the deep lung, with aerodynamic sizes ranging 3.2-3.8µm, and excellent fine particle fraction (FPF) (FPF of 47% for CHT-bearing targeted AuNPs). The optimal biodegradation and release profiles enabled a sustained and controlled release of the embedded nanoparticles, with enhanced cellular uptake, opening new prospects for future lung theragnosis.
Assuntos
Aerossóis/administração & dosagem , Aerossóis/química , Ouro/química , Pulmão/metabolismo , Nanopartículas Metálicas/química , Pós/administração & dosagem , Pós/química , Células A549 , Linhagem Celular Tumoral , Química Farmacêutica/métodos , Quitosana/química , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Inaladores de Pó Seco/métodos , Excipientes/química , Humanos , Nanopartículas Metálicas/administração & dosagem , Tamanho da PartículaRESUMO
The phenomenology of sound speeds in fluid mixtures is examined near and across critical lines. Using literature data for binary and ternary mixtures, it is shown that the ultrasound speed along an isotherm-isopleth passes through a minimum value in the form of an angular (or V-shaped) point at critical states. The relation between critical and pseudo-critical coordinates is discussed. For nonazeotropic fixed-composition fluid mixtures, pseudo-critical temperatures and pressures are found to be lower than the corresponding critical temperatures and pressures. The analysis shows that unstable pseudo-critical states cannot be detected using acoustic methods. The thermodynamic link between sound speeds and isochoric heat capacities is formulated and discussed in terms of p-Vm-T derivatives capable of being calculated using cubic equations of state. Based on the Griffiths-Wheeler theory of critical phenomena, a new specific link between critical sound speeds and critical isochoric heat capacities is deduced in terms of the rate of change of critical pressures and critical temperatures along the p-T projection of the critical locus of binary fluid mixtures. It is shown that the latter link can be used to obtain estimates of critical isochoric heat capacities from the experimental determination of critical speeds of sound. The applicability domain of the new link does not include binary systems at compositions along the critical line for which the rate of change in pressure with temperature changes sign. The new equation is combined with thermodynamic data to provide approximate numerical estimates for the speed of sound in two mixtures of carbon dioxide and ethane at different temperatures along their critical isochores. A clear decrease in the sound speed is found at critical points. A similar behavior is suggested by available critical heat capacity data for several binary fluid mixtures. Using an acoustic technique, the critical temperature and pressure were determined for three different mixtures of methane and propane, and compared with literature data obtained using conventional methods. It is concluded that acoustic-based techniques are reliable to determine, for the most part, critical surfaces of fluid mixtures. The remaining few cases where the present analysis cannot be applied could be tested by the thermodynamic calculation of critical sound speeds using crossover equations of state in conjunction with experimentally determined critical isochoric heat capacities.