Nanoconfinement of a Pharmaceutical Cocrystal with Praziquantel in Mesoporous Silica: The Influence of the Solid Form on Dissolution Enhancement.

Nanoconfinement is a recent strategy to enhance solubility and dissolution of active pharmaceutical ingredients (APIs) with poor biopharmaceutical properties. In this work, we combine the advantage of cocrystals of racemic praziquantel (PZQ) containing a water-soluble coformer (i.e., increased solubility and supersaturation) and its confinement in a mesoporous silica material (i.e., increased dissolution rate). Among various potential cocrystalline phases of PZQ with dicarboxylic acid coformers, the cocrystal with glutaric acid (PZQ-GLU) was selected and successfully loaded by the melting method into nanopores of SBA-15 (experimental pore size of 5.6 nm) as suggested by physical and spectroscopic characterization using various complementary techniques like N2 adsorption, powder X-ray diffraction (PXRD), infrared spectroscopy (IR), solid-state NMR (ss-NMR), differential scanning calorimetry (DSC), and field emission-scanning electron microscopy (FE-SEM) analysis. The PZQ-GLU phase confined in SBA-15 presents more mobility according to ss-NMR studies but still retains its cocrystal-like features in the IR spectra, and it also shows depression of the melting transition temperature in DSC. On the contrary, pristine PZQ loaded into SBA-15 was found only in the amorphous state, according to the aforementioned studies. This dissimilar behavior of the composites was attributed to the larger crystal lattice of PZQ over the PZQ-GLU cocrystal (3320.1 vs 1167.9 Å3) and to stronger intermolecular interactions between PZQ and GLU, facilitating the confinement of a more mobile solid-like phase in the constrained channels. Powder dissolution studies under extremely nonsink conditions (SI = 0.014) of the confined PZQ-GLU and amorphous PZQ phases embedded in mesoporous silica showed transient supersaturation behavior when dissolving in simulated gastric fluid (HCl pH 1.2 at 37 ± 0.5 °C) in a similar fashion to the bare cocrystal PZQ-GLU. A comparison of the area under the curve (AUC0-90 min) of the dissolution profiles afforded a dissolution advantage of 2-fold (p < 0.05) of the new solid phases over pristine racemic PZQ after 90 min; under these conditions, the solubilized API reprecipitated as the recently discovered PZQ hemihydrate (PZQ-HH). In the presence of a cellulosic polymer, sustained solubilization of PZQ from composites SBA-15/PZQ or SBA-15/PZQ-GLU was observed, increasing AUC0-90 min up to 5.1-fold in comparison to pristine PZQ. The combination of a confined solid phase in mesoporous silica and a methylcellulose polymer in the dissolution medium effectively maintained the drug solubilized during times significant to promote absorption. Finally, powder dissolution studies under intermediate nonsink conditions (SI = 1.99) showed a fast release profile from the nanoconfined PZQ-GLU phase in SBA-15, which reached rapid saturation (95% drug dissolved at 30 min); the amorphous PZQ composite and bare PZQ-GLU also displayed an immediate release of the API but at a lower rate (69% drug dissolved at 30 min). In all of these cases, a large dissolution advantage was observed from any of the novel solid phases over PZQ.

A poly (saccharide-ester-urethane) scaffold for mammalian cell growth.

Chitosan and poly(3-hydroxybutyrate) are non-toxic, biodegradable, and biocompatible polymers extensively used in regenerative medicine. However, it is unknown whether the chemical combination of these polymers can produce a biomaterial that induces an appropriate cellular response in vitro in mammalian cells. This study aimed to test the ability of a novel salt-leached polyurethane scaffold of chitosan grafted with poly(3-hydroxybutyrate) to support the growth of three mammalian cell lines of different origin: a) HEK-293 cells, b) i28 mouse myoblasts, and c) human dermal fibroblasts. The viability of the cells was assessed by either evaluation of their capacity to maintain the expression of the green fluorescent protein by adenoviral transduction or by esterase activity and plasma membrane integrity. The results indicated that the three cell lines attached well to the scaffold; however, when i28 cells were induced to differentiate, they did not produce morphologically distinct myofibers, and cell growth ceased. In conclusion, the findings reveal that, altogether, these observations suggest that this foam scaffold supports cell growth and proliferation but may not apply to all cell types. Hence, one crucial question yet to be resolved is a poly (saccharide-ester-urethane) derivative with a nano-topography that elicits a similar cellular response for different biological environments.

Identification of the preferential CO and SO2 adsorption sites within NOTT-401.

NOTT-401 was found to be a highly stable adsorbent for SO2 and CO with excellent cyclability and a straightforward regeneration at room temperature. Moreover, the preferential CO binding sites within the MOF material have been identified by experimental in situ DRIFT spectroscopy coupled with DFT and QTAIM calculations. Such preferential CO adsorption sites were correlated to identify the most significant SO2 interactions within NOTT-401. This study sheds light on the role of the thiophene and hydroxo functionality, for a MOF material, in the binding of SO2 or CO.

SO2 Capture Using Porous Organic Cages.

We report the first experimental investigation of porous organic cages (POCs) for the demanding challenge of SO2 capture. Three structurally related N-containing cage molecular materials were studied. An imine-functionalized POC (CC3) showed modest and reversible SO2 capture, while a secondary-amine POC (RCC3) exhibited high but irreversible SO2 capture. A tertiary amine POC (6FT-RCC3) demonstrated very high SO2 capture (13.78 mmol g-1 ; 16.4 SO2 molecules per cage) combined with excellent reversibility for at least 50 adsorption-desorption cycles. The adsorption behavior was investigated by FTIR spectroscopy, 13 C CP-MAS NMR experiments, and computational calculations.

Comprehensive mapping of human body skin hydration: A pilot study.

BACKGROUND: Previous studies analyzed a series of representative anatomical regions in the human body; however, there is a wide structural and cellular variability in the constitution of the skin. Our objective was to perform a comprehensive assessment of human skin hydration throughout the largest possible area. MATERIALS AND METHODS: Hydration was registered by Corneometer® CM825 probe in 23 anatomical regions of five healthy men. Each zone was analyzed by 2-cm segments in the supine, prone, and lateral positions. A total of 7863 measurements were registered. RESULTS: Differences in the degree of hydration among the prone, supine, and lateral regions were observed. The chest and back showed a pattern of increased hydration toward the neck area. Higher levels of hydration were evidenced in the proximal areas and in the regions near the elbow and knee. The regions of greater mechanical wear and with greater exposure to the sun exhibited a lower degree of hydration. CONCLUSION: The human skin exhibited hydration patterns influenced by anatomical function and the degree of sun exposure. Detailed information of the hydration patterns could serve as reference for the design of topical products, as an indicator of their effectiveness, and for the monitoring of skin pathologies.

Copper release by MOF-74(Cu): a novel pharmacological alternative to diseases with deficiency of a vital oligoelement.

Copper deficiency can trigger various diseases such as Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and even compromise the development of living beings, as manifested in Menkes disease (MS). Thus, the regulated administration (controlled release) of copper represents an alternative to reduce neuronal deterioration and prevent disease progression. Therefore, we present, to the best of our knowledge, the first experimental in vitro investigation for the kinetics of copper release from MOF-74(Cu) and its distribution in vivo after oral administration in male Wistar rats. Taking advantage of the abundance and high periodicity of copper within the crystalline-nanostructured metal-organic framework material (MOF-74(Cu)), it was possible to control the release of copper due to the partial degradation of the material. Thus, we simultaneously corroborated a low accumulation of copper in the liver (the main detoxification organ) and a slight increase of copper in the brain (striatum and midbrain), demonstrating that MOF-74(Cu) is a promising pharmacological alternative (controlled copper source) to these diseases.

Copper(II)-MOFs for bio-applications.

The recent development and implementation of copper-based metal-organic frameworks in biological applications are reviewed. The advantages of the presence of copper in MOFs for relevant applications such as drug delivery, cancer treatment, sensing, and antimicrobial are highlighted. Advanced composites such as MOF-polymers are playing critical roles in developing materials for specific applications.

Combined use of novel chitosan-grafted N-hydroxyethyl acrylamide polyurethane and human dermal fibroblasts as a construct for in vitro-engineered skin.

A rich plethora of information about grafted chitosan (CS) for medical use has been reported. The capability of CS-grafted poly(N-hydroxyethyl acrylamide) (CS-g-PHEAA) to support human dermal fibroblasts (HDFs) in vitro has been proven. However, CS-grafted copolymers lack good stiffness and the characteristic microstructure of a cellular matrix. In addition, whether CS-g-PHEAA can be used to prepare a scaffold with a suitable morphology and mechanical properties for skin tissue engineering (STE) is unclear. This study aimed to show for the first time that step-growth polymerizations can be used to obtain polyurethane (PU) platforms of CS-g-PHEAA, which can also have enhanced microhardness and be suitable for in vitro cell culture. The PU prepolymers were prepared from grafted CS, polyethylene glycol, and 1,6-hexamethylene diisocyanate. The results proved that a poly(saccharide-urethane) [(CS-g-PHEAA)-PU] could be successfully synthesized with a more suitable microarchitecture, thermal properties, and topology than CS-PU for the dynamic culturing of fibroblasts. Cytotoxicity, proliferation, histological and immunophenotype assessments revealed significantly higher biocompatibility and cell proliferation of the derivative concerning the controls. Cells cultured on (CS-g-PHEAA)-PU displayed a quiescent state compared to those cultured on CS-PU, which showed an activated phenotype. These findings may be critical factors in future studies establishing wound dressing models.

SU-101: a Bi(III)-based metal-organic framework as an efficient heterogeneous catalyst for the CO2 cycloaddition reaction.

A non-porous version of SU-101 (herein n-SU-101) was evaluated for the CO2 cycloaddition reaction. The findings revealed that open metal sites (Bi3+) are necessary for the reaction. n-SU-101 displays a high styrene oxide conversion of 96.6% under mild conditions (3 bar and 80 °C). The catalytic activity of n-SU-101 demonstrated its potential application for the cycloaddition of CO2 using styrene oxide.

Fluorinated hydrotalcites: the addition of highly electronegative species in layered double hydroxides to tune basicity.

Hydrotalcite-like compounds were synthesized by coprecipitation using a constant-pH method. Aluminum was introduced in the form of an octahedral aluminum fluorine complex during the synthesis. Controlling the pH during the synthesis ensured that aluminum fluorine did not decompose to tetrahedral species but remained in the octahedral (AlF(6))(3-) form to be incorporated into brucite-like sheets. The physicochemical, thermal, and spectroscopic characterizations showed significant modifications by fluorine introduction regarding structural, textural, and adsorption properties. The memory effect of fluorinated hydrotalcites differed from the memory effect commonly observed in fluorine-free hydrotalcites. Nitromethane adsorption showed that the basicity of hydrotalcite was greatly modified by the fluorine loading.

Structural and thermochemical chemisorption of CO2 on Li(4+x)(Si(1-x)Al(x))O4 and Li(4-x)(Si(1-x)V(x))O4 solid solutions.

Different Li(4)SiO(4) solid solutions containing aluminum (Li(4+x)(Si(1-x)Al(x))O(4)) or vanadium (Li(4-x)(Si(1-x)V(x))O(4)) were prepared by solid state reactions. Samples were characterized by X-ray diffraction and solid state nuclear magnetic resonance. Then, samples were tested as CO(2) captors. Characterization results show that both, aluminum and vanadium ions, occupy silicon sites into the Li(4)SiO(4) lattice. Thus, the dissolution of aluminum is compensated by Li(1+) interstitials, while the dissolution of vanadium leads to lithium vacancies formation. Finally, the CO(2) capture evaluation shows that the aluminum presence into the Li(4)SiO(4) structure highly improves the CO(2) chemisorption, and on the contrary, vanadium addition inhibits it. The differences observed between the CO(2) chemisorption processes are mainly correlated to the different lithium secondary phases produced in each case and their corresponding diffusion properties.

Sc(III)-Based metal-organic frameworks.

Scandium(III) ions can form robust metal-organic frameworks (MOFs) with relative ease of synthesis. However, their use in MOF construction remains scarce compared to the vast collection of MOFs using other ions. This highlight features the chronological development of Sc(III)-MOFs, which attest to the ability of Sc(III) ions to afford materials that combine exceptional stability with catalytic or photo-physical attributes.

Coloured hybrid materials: exploiting an emergent surface property of fluorinated Al2O3 containing anthocyanins and betacyanins.

Two fluorinated γ-Al2O3 series were synthesized by a sol-gel method with two solvents (2-propanol and 2-butanol), two aluminium sources (ATB and ATP) and one fluorine source (Na3AlF6). The resulting inorganic matrixes were evaluated to characterize aluminium and fluorine species ([AlO45-], [AlO57-], [AlO69-], [AlF4-], [AlF52-] and [AlF63-]) by powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), 27Al magic angle spinning nuclear magnetic resonance (27Al MAS-NMR) and infrared spectroscopy (IR-ATR). BET and BJH analyses using the nitrogen isotherms of these materials allowed identifying a clear trend in some textural parameters such as specific surface area and fluorine content. These results were confirmed by scanning electron microscopy (SEM). Chemical affinity and acid surface properties were evidenced with colour shifts in two groups of hybrid pigments, prepared with natural anthocyanins (Brassica oleracea) and betacyanins (Bougainvillea glabra).

Linezolid@MOF-74 as a host-guest system with antimicrobial activity.

Linezolid (LNZ) is a new-generation synthetic molecule for the antibacterial treatment of severe infections, particularly in infective cases where the bacterial resistance to first-choice drugs is caused by Gram-positive pathogens. In this context, since 2009, some strains resistant to LNZ in patients with long-term treatments have been reported. Therefore, there is a need to use not only new drug molecules with antibacterial activities in the dosage form but also a different approach to pharmacotherapeutic strategies for skin infections, which lead to a reduction in the concentration of biocides. This work explores LNZ hosted at two isostructural MOFs, MOF-74(Zn) and MOF-74(Cu), as promising antimicrobial systems for gradual biocide release within 6 h. These systems reach a lower minimum inhibitory concentration (MIC) in comparison to free LNZ. Even a decreased MIC value is also observed, which is an encouraging result regarding the efficiency of the systems to control concentration-dependent antimicrobial resistance.

Gold nanoparticles: current and upcoming biomedical applications in sensing, drug, and gene delivery.

Gold nanoparticles (AuNPs) present unique physicochemical characteristics, low cytotoxicity, chemical stability, size/morphology tunability, surface functionalization capability, and optical properties which can be exploited for detection applications (colorimetry, surface-enhanced Raman scattering, and photoluminescence). The current challenge for AuNPs is incorporating these properties in developing more sensible and selective sensing methods and multifunctional platforms capable of controlled and precise drug or gene delivery. This review briefly highlights the recent progress of AuNPs in biomedicine as bio-sensors and targeted nano vehicles.

Discovering the effect of solvents on poly(2-aminoethyl methacrylate) grafting onto chitosan for an in vitro skin model.

The design of controlled grafting copolymers is critical in synthesizing effective artificial cellular matrices because of their regulatory role in cellular behavior. However, it is unclear whether poly(2-aminoethyl methacrylate) grafted onto chitosan generated by gamma-radiation-induced graft polymerization in different solvents can influence the physicochemical properties and biotech applicability of the copolymer. This work aims to demonstrate for the first time the effect of various solvents on the synthesis, properties, and biological performance of grafted chitosan using the simultaneous irradiation method. The results proved that the solvent is one of the critical factors affecting the properties of the modified polysaccharide. The degree of grafting showed a solvent-dependent profile. Hexane presented utmost importance concerning the degree of grafting. Ethyl acetate showed the best results in grafting extent and human dermal fibroblast growth. These findings indicate that proper solvent selection determines the possible copolymer use for in vitro engineered skin substitute models.

CO2 capture at low temperatures (30-80 °C) and in the presence of water vapor over a thermally activated Mg-Al layered double hydroxide.

The carbonation process of a calcined Mg-Al layered double hydroxide (LDH) was systematically analyzed at low temperatures, varying the relative humidity. Qualitative and quantitative experiments were performed. In a first set of experiments, the relative humidity was varied while maintaining a constant temperature. Characterization of the rehydrated products by thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR) and solid-state NMR revealed that the samples did not recover the LDH structure; instead hydrated MgCO(3) was produced. The results were compared with similar experiments performed on magnesium oxide for comparison purposes. Then, in the second set of experiments, a kinetic analysis was performed. The results showed that the highest CO(2) capture was obtained at 50 °C and 70% of relative humidity, with a CO(2) absorption capacity of 2.13 mmol/g.

Critical Thickness of Free-Standing Nanothin Films Made of Melted Polyethylene Chains via Molecular Dynamics.

The mechanical stability of nanothin free-standing films made of melted polyethylene chains was predicted via molecular dynamics simulations in the range of 373.15-673.15 K. The predicted critical thickness, tc, increased with the square of the temperature, T, with additional chains needed as T increased. From T = 373.15 K up to the thermal limit of stability for polyethylene, tc values were in the range of nanothin thicknesses (3.42-5.63 nm), which approximately corresponds to 44-55 chains per 100 nm2. The density at the center of the layer and the interfacial properties studied (density profiles, interfacial thickness, and radius of gyration) showed independence from the film thickness at the same T. The polyethylene layer at its tc showed a lower melting T (<373.15 K) than bulk polyethylene.

Cation folding and the thermal stability limit of the ionic liquid [BMIM+][BF4 -] under total vacuum.

Molecular dynamics simulations reveal the behavior of the bimodal distribution of cation conformations (folded/unfolded) in ionic liquids based on alkylated imidazoles, such as [BMIM+][BF4 -]. The alkyl chains of the cations can fold and block interactions between the cations and anions, thereby reducing the cohesivity of the liquid. At room temperature, the folded conformations represent less than one-third of the total conformations. In contrast to the behavior observed during the thermal denaturation of proteins, in ionic liquids, the concentration of folded cations grows when the temperature increases. At the equimolar concentration, the system reaches the reported experimental temperature of thermal stability (similar to the thermal denaturation behavior). There is an outermost layer of cations at the interface that can tilt toward the interface and cover a layer of anions adsorbed at the interface. This interfacial conformation makes the system stable in transverse directions and unstable in the normal direction at temperatures in the region of thermal instability, limiting the rate of vaporization of neutral ion pairs, which are observed as rare events at temperatures as low as 773.15 K.

Fluorinated MIL-101 for carbon capture utilisation and storage: uptake and diffusion studies under relevant industrial conditions.

Carbon capture utilisation and storage (CCUS) using solid sorbents such as zeolites, activated carbon and Metal-Organic Frameworks (MOFs) could facilitate the reduction of anthropogenic CO2 concentration. Developing efficient and stable adsorbents for CO2 capture as well as understanding their transport diffusion limitations for CO2 utilisation plays a crucial role in CCUS technology development. However, experimental data available on CO2 capture and diffusion under relevant industrial conditions is very limited, particularly for MOFs. In this study we explore the use of a gravimetric Dynamic Vapour Sorption (DVS) instrument to measure low concentration CO2 uptake and adsorption kinetics on a novel partially fluorinated MIL-101(Cr) saturated with different water vapour concentrations, at ambient pressure and temperature. Results show that up to water P/P 0 = 0.15 the total CO2 uptake of the modified material improves and that the introduction of small amounts of water enhances the diffusion of CO2. MIL-101(Cr)-4F(1%) proved to be a stable material under moist conditions compared to other industrial MOFs, allowing facile regeneration under relevant industrial conditions.