Interfacial tension of ethanol, water, and their mixtures in high pressure carbon dioxide: Measurements and modeling.

HYPOTHESIS: It is particularly noteworthy to study interfacial tension behavior under pressurized carbon dioxide for supercritical processes such as crystallization or fractionation. For the latter, a liquid phase and a supercritical phase are in contact, and interfacial properties influence mass transfer phenomena and hydrodynamics. Ethanol-water mixture is a good theoretical study case also involved in a wide range of applications. EXPERIMENTAL: Interfacial tensions of ethanol, water and three mixtures, with an ethanol mass fraction from 0.25 to 0.75, under pressurized CO2 were measured for pressures ranging from 0.1 MPa to 15.1 MPa at 313.15 K and 333.15 K. A specific experimental set-up was used for CO2 phase saturation. FINDINGS: This work brings interfacial tension data of five different solutions including water and ethanol in contact with CO2. Effects of pressure, temperature, carbon dioxide density and ethanol mass fraction are discussed regarding the literature. Significant discrepancies are found with previous literature data for ethanol-water mixtures. The "two-step" decrease observed when pressure or density increase is also discussed regarding both the concept of Widom line, and the polar and dispersive contributions of the surface tension of a component. For the first time, fair accurate interfacial tension modeling involving these contributions is addressed.

Correction: Galenic lab-on-a-chip concept for lipid nanocapsules production.

Correction for 'Galenic Lab-on-a-Chip concept for lipid nanocapsules production' by Nicolas Rolley et al., Nanoscale, 2021, 13, 11899-11912, DOI: 10.1039/D1NR00879J.

Galenic Lab-on-a-Chip concept for lipid nanocapsules production.

The continuous production of drug delivery systems assisted by microfluidics has drawn a growing interest because of the high reproducibility, low batch-to-batch variations, narrow and controlled particle size distributions and scale-up ease induced by this kind of processes. Besides, microfluidics offers opportunities for high throughput screening of process parameters and the implementation of process characterization techniques as close to the product as possible. In this context, we propose to spotlight the GALECHIP concept through the development of an instrumented microfluidic pilot considered as a Galenic Lab-on-a-Chip to formulate nanomedicines, such as lipid nanocapsules (LNCs), under controlled process conditions. In this paper we suggest an optimal rational development in terms of chip costs and designs. First, by using two common additive manufacturing techniques, namely fused deposition modelling and multi-jet modelling to prototype customized 3D microfluidic devices (chips and connectors). Secondly, by manufacturing transparent Silicon (Si)/Glass chips with similar channel geometries but obtained by a new approach of deep reactive ion etching (DRIE) technology suitable with in situ small angle X-ray scattering characterizations. LNCs were successfully produced by a phase inversion composition (PIC) process with highly monodispersed sizes from 25 nm to 100 nm and formulated using chips manufactured by 3D printing and DRIE technologies. The transparent Si/Glass chip was also used for the small angle X-ray scattering (SAXS) analysis of the LNC formulation with the PIC process. The 3D printing and DRIE technologies and their respective advantages are discussed in terms of cost, easiness to deploy and process developments in a GALECHIP point of view.

The advantages of nanomedicine in the treatment of visceral leishmaniasis: between sound arguments and wishful thinking.

Introduction: Although life-threatening if left untreated, visceral leishmaniasis (VL) is still a neglected endemic disease in 98 countries worldwide. The number of drugs available is low and few are in clinical trials. In the last decades, efforts have been made on the development of nanocarriers as drug delivery systems to treat VL. Given the preferential intracellular location of the parasite in the liver and spleen macrophages, the rationale is sturdy. In a clinical setting, liposomal amphotericin B displays astonishing cure rates.Areas covered: A literature search was performed through PubMed and Google Scholar. We critically reviewed the main literature highlighting the success of nanomedicine in VL. We also reviewed the hurdles and yet unfulfilled promises rising awareness of potential drawbacks of nanomedicine in VL.Expert opinion: VL is a disease where nanomedicines successes shine through. However, there are a lot of obstacles on the road to developing more efficient strategies such as targeting functionalization, oral formulations, or combined therapies. And those strategies raise many questions.

Synthesis of PDMS-b-POEGMA Diblock Copolymers and Their Application for the Thermoresponsive Stabilization of Water-Supercritical Carbon Dioxide Emulsions.

In this study, PDMS13-b-POEGMAx diblock copolymers consisting of a CO2-philic poly(dimethylsiloxane) (PDMS) block connected to a thermosensitive hydrophilic poly(oligoethylene glycol methacrylate) (POEGMA) block were synthesized by reversible addition-fragmentation chain-transfer (RAFT) radical polymerization. Their ability to decrease the water-supercritical CO2 (scCO2) interfacial tension (γ) and to stabilize water-scCO2 emulsions was investigated using an original homemade device developed in the laboratory. This device is able to control the pressure from 1 to 250 bar and the temperature from 40 to 80 °C. It was implemented with 2 visualization windows, a drop tensiometer and a remote optical head for dynamic light scattering (DLS) measurements. These experiments revealed that PDMS-b-POEGMA decreased γ down to 1-2 mN/m and was the most efficient at high pressure (250 bar) and low temperature (40 °C) where PDMS and POEGMA blocks exhibited the highest affinity for their respective phase. The diblock copolymers were shown to stabilize water-scCO2 emulsions. Moreover, the thermosensitive behavior of the POEGMA block in water (with a lower critical solubility temperature around 65 °C) resulted in the formation of temperature-responsive emulsions that could reversibly switch at 100 bar from stable at 40 °C to unstable at 80 °C. These results were rationalized based on the solubility of each individual block of the copolymers in water and scCO2 as a function of temperature and pressure.

Importance of Combining Advanced Particle Size Analysis Techniques To Characterize Cell-Penetrating Peptide-Ferrocifen Self-Assemblies.

The design of a simple platform to target the delivery of notably hydrophobic drugs into cancer cells is an ultimate goal. Here, three strategies were combined in the same nanovector, in limiting the use of excipients: cell-penetrating peptides, an amphiphilic prodrug, and self-assembly. Light scattering and cryogenic transmission electron microscopy revealed one size population of objects around 100 nm with a narrow size distribution. However, in-depth analysis of the suspension by nanoparticle tracking analysis, small-angle X-ray scattering, and nuclear magnetic resonance (NMR) diffusometry demonstrated the presence of another population of small objects (<2 nm). It has been shown that these small self-assemblies represented >99% of the matter! This presence was clearly and unambiguously demonstrated by NMR diffusometry experiments. The study highlights the importance and the complementary contribution of each characterization method to reflect the reality of the studied nanoassembly.

Protein encapsulation and release from PEO-b-polyphosphoester templated calcium carbonate particles.

Calcium carbonate particles are promising candidates as proteins carriers for their controlled delivery in the body. The present paper aims at investigating the protein encapsulation by in situ precipitation of calcium carbonate particles prepared by a process based on supercritical CO2 and using a new type of degradable well-defined double hydrophilic block copolymers composed of poly(ethylene oxide) and polyphosphoester blocks acting as templating agent for the calcium carbonate. For this study, lysozyme was chosen as a model for therapeutic protein for its availability and ease of detection. It was found that by this green process, loading into the CaCO3 microparticles with a diameter about 2µm can be obtained as determined by scanning electron microscopy. A protein loading up to 6.5% active lysozyme was measured by a specific bioassay (Micrococcus lysodeikticus). By encapsulating fluorescent-labelled lysozyme (lysozyme-FITC), the confocal microscopy images confirmed its encapsulation and suggested a core-shell distribution of lysozyme into CaCO3, leading to a release profile reaching a steady state at 59% of release after 90min.

Implementation of in situ SAXS/WAXS characterization into silicon/glass microreactors.

A successful implementation of in situ X-ray scattering analysis of synthetized particle materials in silicon/glass microreactors is reported. Calcium carbonate (CaCO3) as a model material was precipitated inside the microchannels through the counter-injection of two aqueous solutions, containing carbonate ions and calcium ions, respectively. The synthesized calcite particles were analyzed in situ in aqueous media by combining Small Angle X-ray Scattering (SAXS) and Wide Angle X-ray Scattering (WAXS) techniques at the ESRF ID02 beam line. At high wavevector transfer, WAXS patterns clearly exhibit different scattering features: broad scattering signals originating from the solvent and the glass lid of the chip, and narrow diffraction peaks coming from CaCO3 particles precipitated rapidly inside the microchannel. At low wavevector transfer, SAXS reveals the rhombohedral morphology of the calcite particles together with their micrometer size without any strong background, neither from the chip nor from the water. This study demonstrates that silicon/glass chips are potentially powerful tools for in situ SAXS/WAXS analysis and are promising for studying the structure and morphology of materials in non-conventional conditions like geological materials under high pressure and high temperature.

Preparation of polymeric particles in CO2 medium using non-toxic solvents: discussions on the mechanism of particle formation.

The aim of this work was to develop a novel formulation method, termed modified-PGSS (modified-Particle from Gas Saturated Solution), for the encapsulation of protein into polymeric microparticles in CO2 medium. In this study, isosorbide dimethyl ether (DMI), a non-toxic water-miscible solvent, was used for the formulation and lysozyme was chosen as a model protein for encapsulation into PLGA microparticles. First, the mechanism of particle formation has been extensively studied and was discussed in detail. Phase behavior was investigated by measuring the solubility of CO2 in DMI and volumetric expansion of DMI saturated in CO2. Here, we demonstrate the consistency of the experimental values with the data obtained from the mathematical (such as the neural network) and thermodynamic (such as the Peng-Robinson equation of state) models. These models were built to develop predictive tools in the chosen experimental space for microparticle formulation. Furthermore, these microparticles were characterized in terms of size and zeta potential. The morphology and protein distribution within PLGA microparticles were determined using scanning electron microscopy and confocal microscopy, respectively. High encapsulation efficiency (65%) was obtained as confirmed by lysozyme quantification using a specific bioassay (M. lysodeikticus). Moreover, the in vitro protein release profile from loaded microparticles was presented. In this study, we report an innovative and green process for lysozyme encapsulation into PLGA microparticles. Thus, this process could be applied to the encapsulation of therapeutic proteins requiring protection and controlled release such as growth factors for regenerative medicine.

Synthesis and characterization of CaCO3-biopolymer hybrid nanoporous microparticles for controlled release of doxorubicin.

Doxorubicin (Dox) is a hydrophilic drug extensively used for treatment of breast, lung, and ovarian cancer, among others; it is highly toxic and can cause serious side effects on nontargeted tissues. We developed and studied a hybrid nanoporous microparticle (hNP) carrier based on calcium carbonate and biopolymers derivatized with folic acid (FA) and containing Dox as a chemotherapeutic drug model. The hNPs were characterized by X-ray diffraction, and Raman and Fourier transform infrared (FTIR) spectroscopies. The X-ray diffraction patterns of calcium carbonate particles showed about 30-70% vaterite-calcite polymorphisms and up to 95% vaterite, depending on the absence or the presence of biopolymers as well as their type. Scanning electron microcopy images revealed that all types of hNPs were approximately spherical and porous with average diameter 1-5 µm, and smaller than CaCO3 microparticles. The presence of biopolymers in the matrices was confirmed after derivatization with a fluorescein isothiocyanate probe by means of confocal microscopy and FTIR synchrotron beamline analysis. In addition, the coupling of lambda carrageenan (λ-Car) to FA in the microparticles (FA-λ-Car-hNPs) increased the cancer-cell targeting and also extended the specific surface area by up to ninefold (26.6 m2 g(-1)), as determined by the Brunauer-Emmett-Teller isotherm. A nanostructured porous surface was found in all instances, and the FA-λ-Car-hNP pore size was about 30 nm, as calculated by means of the Barrett-Joyner-Halenda adsorption average. The test of FA-λ-Car-hNP anticancer activity on human osteosarcoma MG-63 cell line showed cell viabilities of 13% and 100% with and without Dox, respectively, as determined by crystal violet staining after 24 h of incubation.

Quantification of the dissolved inorganic carbon species and of the pH of alkaline solutions exposed to CO2 under pressure: a novel approach by Raman scattering.

Dissolved inorganic carbon (DIC) content of aqueous systems is a key function of the pH, of the total alkanility (TA), and of the partial pressure of CO2. However, common analytical techniques used to determine the DIC content in water are unable to operate under high CO2 pressure. Here, we propose to use Raman spectroscopy as a novel alternative to discriminate and quantitatively monitor the three dissolved inorganic carbon species CO2(aq), HCO3(-), and CO3(2-) of alkaline solutions under high CO2 pressure (from P = 0 to 250 bar at T = 40 °C). In addition, we demonstrate that the pH values can be extracted from the molalities of CO2(aq) and HCO3(-). The results are in very good agreement with those obtained from direct spectrophotometric measurements using colored indicators. This novel method presents the great advantage over high pressure conventional techniques of not using breakable electrodes or reference additives and appears of great interest especially in marine biogeochemistry, in carbon capture and storage and in material engineering under high CO2 pressure.

Surface activity of a fluorinated carbohydrate ester in water/carbon dioxide emulsions.

The water/carbon dioxide (W/CO2) interfacial activity and emulsifying capacity of hydrocarbon and fluorinated carbohydrate esters are investigated of the first time and compared to the performance of sodium-bis(2-ethylhexyl)sulfosuccinate (AOT). The reduction of the W/CO2 interfacial tension was measured using a pendant drop tensiometer equipped with a cell view pressurized with CO2 at 80 bar and 45°C. It was found that the interface stabilization improved in the order AOT<6-O-myristoyl mannose<6-O-(2H,2H,3H,3H-perfluoroundecanoyl)-D-mannose. In the latter case, a drastic reduction of the W/CO2 interfacial tension was observed (85% reduction, interfacial tension at the equilibrium=3.6 mN/m), which emphasizes the advantage of using a fluorinated CO2-philic tail and the potential of sugars as hydrophilic head. The formulation of stable W/CO2 emulsions was also achieved using the fluorinated mannose derivative. This study paves the way to the design of a novel class of competitive surface active agents for W/CO2 emulsions.

Lysozyme encapsulation into nanostructured CaCO3 microparticles using a supercritical CO2 process and comparison with the normal route.

The aim of the present work was to assess the merits of supercritical CO2 (SC-CO2) as a process for protein encapsulation into calcium carbonate microparticles. Lysozyme, chosen as a model protein, was entrapped during CaCO3 precipitation in two different media: water (normal route) and SC-CO2. The particles were characterized and compared in terms of size, zeta potential, morphology by SEM, crystal polymorph and lysozyme encapsulation. Fluorescent and confocal images suggested the encapsulation and core-shell distribution of lysozyme into CaCO3 obtained by the SC-CO2 process. A high encapsulation efficiency was reached by a supercritical CO2 process (50%) as confirmed by the increased zeta potential value, lysozyme quantification by HPLC and a specific bioassay (M. lysodeikticus). Conversely, lysozyme was scarcely entrapped by the normal route (2%). Thus, supercritical CO2 appears to be an effective process for protein encapsulation within nanostructured CaCO3 particles. Moreover, this process may be used for encapsulation of a wide range of macromolecules and bioactive substances.