The endothelial barrier function is tightly controlled by a broad range of signaling cascades including nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway. It has been proposed that disturbances in NO and cGMP production could interfere with proper endothelial barrier function. In this study, we assessed the effect of interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, on NO and cGMP levels and examined the mechanisms by which NO and cGMP regulate the IFN-gamma-mediated HUVECs hyperpermeability. The flux of fluorescein isothiocyanate-labeled dextran across cell monolayers was used to study the permeability of endothelial cells. Here, we found that IFN-gamma significantly attenuated basal NO concentration and the increased NO levels supplied by a NO donor, sodium nitroprusside (SNP). Besides, application of IFN-gamma also significantly attenuated both the basal cGMP concentration and the increased cGMP production donated by a cell permeable cGMP analogue, 8-bromo-cyclic GMP (8-Br-cGMP). In addition, exposure of the cell monolayer to IFN-gamma significantly increased HUVECs basal permeability. However, L-NAME pretreatment did not suppress IFN-gamma-induced HUVECs hyperpermeability. L-NAME pretreatment followed by SNP or SNP pretreatment partially reduced IFN-gamma-induced HUVECs hyperpermeability. Pretreatment with a guanylate cyclase inhibitor, 6-anilino-5,8-quinolinedione (LY83583), led to a further increase in IFN-gamma-induced HUVECs hyperpermeability. The findings suggest that the mechanism underlying IFN-gamma-induced increased HUVECs permeability is partly related to the inhibition of NO production.
Human serum albumin (HSA) is a superior carrier for delivering extracellular drugs. However, the development of a cell-penetrating HSA remains a great challenge due to its low membrane permeability. We report herein on the design of a series of palmitoyl-poly-arginine peptides (CPPs) and an evaluation of their cell-penetrating effects after forming a complex with HSA for use in intracellular drug delivery. The palmitoyl CPPs forms a stable complex with HSA by anchoring itself to the high affinity palmitate binding sites of HSA. Among the CPPs evaluated, a cyclic polypeptide composed of D-dodecaarginines, palmitoyl-cyclic-(D-Arg)12 was the most effective for facilitating the cellular uptake of HSA by HeLa cells. Such a superior cell-penetrating capability is primarily mediated by macropinocytosis. The effect of the CPP on pharmacological activity was examined using three drugs loaded in HSA via three different methods: a) an HSA-paclitaxel complex, b) an HSA-doxorubicin covalent conjugate and c) an HSA-thioredoxin fusion protein. The results showed that cell-penetrating efficiency was increased with a corresponding and significant enhancement in pharmacological activity. In conclusion, palmitoyl-cyclic-(D-Arg)12/HSA is a versatile cell-penetrating drug delivery system with great potential for use as a nano-carrier for a wide diversity of pharmaceutical applications.
For dental implants, it is vital that an initial soft tissue seal is achieved as this helps to stabilize and preserve the peri-implant tissues during the restorative stages following placement. The study of the implant-soft tissue interface is usually undertaken in animal models. We have developed an in vitro three-dimensional tissue-engineered oral mucosal model (3D OMM), which lends itself to the study of the implant-soft tissue interface as it has been shown that cells from the three-dimensional OMM attach onto titanium (Ti) surfaces forming a biological seal (BS). This study compares the quality of the BS achieved using the three-dimensional OMM for four types of Ti surfaces: polished, machined, sandblasted and anodized (TiUnite). The BS was evaluated quantitatively by permeability and cell attachment tests. Tritiated water (HTO) was used as the tracing agent for the permeability test. At the end of the permeability test, the Ti discs were removed from the three-dimensional OMM and an Alamar Blue assay was used for the measurement of residual cells attached to the Ti discs. The penetration of the HTO through the BS for the four types of Ti surfaces was not significantly different, and there was no significant difference in the viability of residual cells that attached to the Ti surfaces. The BS of the tissue-engineered oral mucosa around the four types of Ti surface topographies was not significantly different.
A quantitative structure-permeability relationship was developed using Artificial Neural Network (ANN) modeling to study penetration across a polydimethylsiloxane membrane. A set of 254 compounds and their experimentally derived maximum steady state flux values used in this study was gathered from the literature. A total of 42 molecular descriptors were calculated for each compound. A genetic algorithm was used to select important molecular descriptors and supervised ANN was used to correlate selected descriptors with the experimentally derived maximum steady-state flux through the polydimethylsiloxane membrane (log J). Calculated molecular descriptors were used as the ANN's inputs and log J as the output. Developed model indicates that molecular shape and size, inter-molecular interactions, hydrogen-bonding capacity of drugs, and conformational stability could be used to predict drug absorption through skin. A 12-descriptor nonlinear computational neural network model has been developed for the estimation of log J values for a data set of 254 drugs. Described model does not require experimental parameters and could potentially provide useful prediction of membrane penetration of new drugs and reduce the need for actual compound synthesis and flux measurements.
The effects of pump speed, cumulative permeate volume and concentration of feed (yeast cells) on the permeate flux have been studied on a batch cross-flow microfiltration process. The experiments were conducted for two different cellulose acetate membrane modules of 0.2 micron and 0.45 micron pore size. A three factor experiment was designed for this purpose and the effect of the operating parameters on the filtration rate was studied by the analysis of variance (ANOVA). It is concluded from the analysis of the experimental data that pump speed has the maximum bearing upon the permeate rate within the operating range of parameters. Fouling conditions were examined in the light of colloids deposition on membranes due to surface interactions. However this paper looks into the relationship and sensitivity of the operating parameters in a cross-flow microfiltration unit rather than exploring the theoretical principles behind the observed phenomena.
Conventional hydrogeologic framework models used to compute ocean island sustainable yields and aquifer storage neglect the complexity of the nearshore and offshore submarine environment. However, the onshore aquifer at the island of Hawai'i exhibits a notable volumetric discrepancy between high-elevation freshwater recharge and coastal discharge. In this study, we present a novel transport mechanism of freshwater moving from onshore to offshore through a multilayer formation of water-saturated layered basalts with interbedded low-permeability layers of ash/soil. Marine electromagnetic imaging reveals ∼35 km of laterally continuous resistive layers that extend to at least 4 km from west of Hawai'i's coastline, containing about 3.5 km3 of freshened water. We propose that this newly found transport mechanism of fresh groundwater may be the governing mechanism in other volcanic islands. In such a scenario, volcanic islands worldwide can use these renewable offshore reservoirs, considered more resilient to climate change-driven droughts, as new water resources.
Lipid membranes serve as effective barriers allowing cells to maintain internal composition differing from that of extracellular medium. Membrane permeation, both natural and artificial, can take place via appearance of transversal pores. The rearrangements of lipids leading to pore formation in the intact membrane are not yet understood in details. We applied continuum elasticity theory to obtain continuous trajectory of pore formation and closure, and analyzed molecular dynamics trajectories of pre-formed pore reseal. We hypothesized that a transversal pore is preceded by a hydrophobic defect: intermediate structure spanning through the membrane, the side walls of which are partially aligned by lipid tails. This prediction was confirmed by our molecular dynamics simulations. Conversion of the hydrophobic defect into the hydrophilic pore required surmounting some energy barrier. A metastable state was found for the hydrophilic pore at the radius of a few nanometers. The dependence of the energy on radius was approximately quadratic for hydrophobic defect and small hydrophilic pore, while for large radii it depended on the radius linearly. The pore energy related to its perimeter, line tension, thus depends of the pore radius. Calculated values of the line tension for large pores were in quantitative agreement with available experimental data.
Membrane distillation (MD) is an attractive technology for the separation of highly saline water used with a polytetrafluoroethylene (PTFE) hollow fiber (HF) membrane. A hydrophobic coating of low-density polyethylene (LDPE) coats the outer surface of the PTFE membrane to resolve membrane wetting as well as increase membrane permeability flux and salt rejection, a critical problem regarding the MD process. LDPE concentrations in coating solution have been studied and optimized. Consequently, the LDPE layer altered membrane morphology by forming a fine nanostructure on the membrane surface that created a hydrophobic layer, a high roughness of membrane, and a uniform LDPE network. The membrane coated with different concentrations of LDPE exhibited high water contact angles of 135.14 ± 0.24 and 138.08 ± 0.01° for membranes M-3 and M-4, respectively, compared to the pristine membrane. In addition, the liquid entry pressure values of LDPE-incorporated PTFE HF membranes (M-1 to M-5) were higher than that of the uncoated membrane (M-0) with a small decrease in the percentage of porosity. The M-3 and M-4 membranes demonstrated higher flux values of 4.12 and 3.3 L m-2 h-1 at 70 °C, respectively. On the other hand, the water permeation flux of 1.95 L m-2 h-1 for M-5 further decreased when LDPE concentration is increased.
This study presents the electromagnetic (EM) characterization of a multiwalled carbon nanotubes (MWCNT)-silver nanoparticles (AgNP)-reinforced poly(vinyl alcohol) (PVA) hybrid nanocomposite fabricated via the solution mixing technique. Primarily, the structure and morphological properties of the PVA/MWCNT-AgNP hybrid nanocomposite are confirmed by X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM). The complex permittivity (ε*) and permeability (μ*), as well as the electromagnetic scattering parameters are measured using a PNA network analyzer equipped with X-band waveguide. The results showed an enhanced permittivity (ε' ≈ 25) value of the hybrid nanocomposite in the frequency range of 8-12 GHz. However, the permeability decreased to almost zero (μ' ≈ 0.4) since the inclusion of AgNP with an average particle size of 40 nm is not susceptible to magnetization and causes higher magnetic losses (tan δμ) than dielectric losses (tan δε). Remarkably, the hybrid nanocomposite reduced transmission of electromagnetic (EM) wave by nearly 60% in comparison to PVA/MWCNT. This is attributed to the enhanced absorption and reflection at the nanotubes, and metal-dielectric interfaces have induced multiple internal reflections owing to the porous structure of the nanocomposite. The prospect of the PVA/MWCNT-AgNP hybrid nanocomposite is favorable as a thin absorbing material for EM shielding applications.
The capacity of crustaceans to biosynthesise long-chain polyunsaturated fatty acids has yet to be fully defined, due to the lack of evidence on the functional activities of enzymes involved in desaturation or elongation of fatty acid substrates. We report here the cloning and in vitro functional analysis of an elongase from the orange mud crab, Scylla olivacea. Sequence and phylogenetic analysis placed the elovl close to the vertebrate Elovl1 and Elovl7 clade, which is distinct from the other remaining five Elovl families. The elongase was also clustered together with several elongases from crustaceans and insects. This elongase showed activities towards 16:1n-7, and at lower rate, linoleic acid (18:2n-6) and linolenic acid (18:3n-3). To our knowledge this is the first description of a functional enzyme involved in biosynthesis of long-chained polyunsaturated fatty acids in a crustacean species. Expression of the S. olivacea elovl7-like mRNA was prominent in stomach, intestine and gill tissues, due to the need to regulate the permeability of epithelial tissue through modification of fatty acid compositions. The implication of our findings, in terms of ability of Crustacea phylum to biosynthesise polyunsaturated fatty acids is discussed.
Neurotherapeutic potentials of Centella asiatica and its reputation to boost memory, prevent cognitive deficits and improve brain functions are widely acknowledged. The plant's bioactive compounds, i.e. asiaticoside, madecassoside and asiatic acid were reported to have central nervous system (CNS) actions, particularly in protecting the brain against neurodegenerative disorders. Hence, it is important for these compounds to cross the blood-brain barrier (BBB) to be clinically effective therapeutics. This study aimed to explore the capability of asiaticoside, madecassoside and asiatic acid to cross the BBB using in vitro BBB model from primary porcine brain endothelial cells (PBECs). Our findings showed that asiaticoside, madecassoside and asiatic acid are highly BBB permeable with apparent permeability (Papp) of 70.61 ± 6.60, 53.31 ± 12.55 and 50.94 ± 10.91 × 10-6 cm/s respectively. No evidence of cytotoxicity and tight junction disruption of the PBECs were observed in the presence of these compounds. Asiatic acid showed cytoprotective effect towards the PBECs against oxidative stress. This study reported for the first time that Centella asiatica compounds demonstrated high capability to cross the BBB, comparable to central nervous system drugs, and therefore warrant further development as therapeutics for the treatment of neurodegenerative diseases.
The development of membrane technology from biopolymer for water filtration has received a great deal of attention from researchers and scientists, owing to the growing awareness of environmental protection. The present investigation is aimed at producing poly(D-lactic acid) (PDLA) membranes, incorporated with nanocrystalline cellulose (NCC) and cellulose nanowhisker (CNW) at different loadings of 1 wt.% (PDNC-I, PDNW-I) and 2 wt.% (PDNC-II PDNW-II). From morphological characterization, it was evident that the nanocellulose particles induced pore formation within structure of the membrane. Furthermore, the greater surface reactivity of CNW particles facilitates in enhancing the surface wettability of membranes due to increased hydrophilicity. In addition, both thermal and mechanical properties for all nanocellulose filled membranes under investigation demonstrated significant improvement, particularly for PDNW-I-based membranes, which showed improvement in both aspects. The membrane of PDNW-I presented water permeability of 41.92 L/m2h, when applied under a pressure range of 0.1-0.5 MPa. The investigation clearly demonstrates that CNWs-filled PDLA membranes fabricated for this investigation have a very high potential to be utilized for water filtration purpose in the future.
The hydrophobic membranes have been widely explored to meet the membrane characteristics for the membrane distillation (MD) process. Inorganic metal oxide nanoparticles have been used to improve the membrane hydrophobicity, but limited studies have used nano clay particles. This study introduces halloysite nanotube (HNT) as an alternative material to synthesis a hydrophobic poly(vinylidene fluoride) (PVDF)-HNT membrane. The PVDF membranes were fabricated using functionalized HNTs (e.g., carnauba wax and 1H,1H,2H,2H-perfluorooctyl-trichlorosilane (FOTS)). The results were determined by Fourier transform infrared-attenuated total reflection, scanning electron microscope, goniometer and porometer to determine the desired hydrophobic membrane for direct contact membrane distillation (DCMD). The addition of FOTS-HNT (fs-HNT) and carnauba wax-HNT (fw-HNT) in the PVDF membrane enhanced the water contact angle (CA) to 127° and 137°, respectively. The presence of fw-HNT in the PVDF membrane exhibited higher liquid entry pressure (LEP) (2.64 bar) compared to fs-HNT in the membrane matrix (1.44 bar). The PVDF/fw-HNT membrane (Pfw-HNT) obtained the highest flux of 7.24 L/m2h with 99.9% salt removal. A stable permeability in the Pfw-HNT membrane was obtained throughout 16 h of DCMD. The incorporation of fw-HNT in the PVDF membrane had improved the anti-wetting properties and the membrane performance with the anti-fouling effect.
Wastewater containing oil/water emulsion has a serious ecological impact and threatens human health. The impact worsens as its volume increases. Oil/water emulsion needs to be treated before it is discharged or reused again for processing. A membrane-based process is considered attractive in effectively treating oil/water emulsion, but progress has been dampened by the membrane fouling issue. The objective of this study is to develop polyvinylidene fluoride (PVDF) membranes customized for oil/water emulsion separation by incorporating assembly of tannic acid (TA) and polyvinylpyrrolidone (PVP) in the polymer matrix. The results show that the assembly of TA/PVP complexation was achieved as observed from the change in colour during the phase inversion and as also proven from the characterization analyses. Incorporation of the TA/PVP assembly leads to enhanced surface hydrophilicity by lowering the contact angle from 82° to 47°. In situ assembly of the TA/PVP complex also leads to enhanced clean water permeability by a factor of four as a result of enhanced mean flow pore size from 0.2 to 0.9 µm. Owing to enhanced surface chemistry and structural advantages, the optimum hydrophilic PVDF/TA/PVP membrane poses permeability of 540.18 L/(m2 h bar) for oil/water emulsion filtration, three times higher than the pristine PVDF membrane used as the reference.
Recently, many scientists and polymer engineers have been working on eco-friendly materials for starch-based food packaging purposes, which are based on biopolymers, due to the health and environmental issues caused by the non-biodegradable food packaging. However, to maintain food freshness and quality, it is necessary to choose the correct materials and packaging technologies. On the other hand, the starch-based film's biggest flaws are high permeability to water vapor transfer and the ease of spoilage by bacteria and fungi. One of the several possibilities that are being extensively studied is the incorporation of essential oils (EOs) into the packaging material. The EOs used in food packaging films actively prevent inhibition of bacteria and fungi and have a positive effect on food storage. This work intended to present their mechanical and barrier properties, as well as the antimicrobial activity of anti-microbacterial agent reinforced starch composites for extending product shelf life. A better inhibition of zone of antimicrobial activity was observed with higher content of essential oil. Besides that, the mechanical properties of starch-based polymer was slightly decreased for tensile strength as the increasing of essential oil while elongation at break was increased. The increasing of essential oil would cause the reduction of the cohesion forces of polymer chain, creating heterogeneous matrix and subsequently lowering the tensile strength and increasing the elongation (E%) of the films. The present review demonstrated that the use of essential oil represents an interesting alternative for the production of active packaging and for the development of eco-friendly technologies.
Studies on the potential effect of EMF exposure on permeability of the blood-brain barrier (BBB) in humans are virtually absent. This study was conducted to study the effect of EMF exposure on pericytes in brain tissues and its effect on oxidative stress level in the blood through total protein and malondialdehyde (MDA). About 16 male rats (Wistar) were used and divided into two groups which were negative control and treatment group. In negative control group, the animals were placed in a solenoid without any EMF exposure for 3 hours daily for 5 days. In the treatment group, the animals were placed in a solenoid with 0.3 mT EMF exposure for the same time duration. On day 3 and day 5, animals were sacrificed and the brain was removed for histological examination while on day 1, day 3 and day 5, the blood was collected for biochemistry analysis. Histological observation showed the presence of morphological changes in the brain tissues of rats that exposed to EMF. Statistical analysis showed that there is no significant decrease in total protein (p>0.05) between negative control group and treatment group. Meanwhile, MDA level in blood showed a significant increase in treatment group (p
This review highlights in vitro drug dissolution/permeation methods available for topical and transdermal nanocarriers that have been designed to modulate the propensity of drug release, drug penetration into skin, and permeation into systemic circulation. Presently, a few of USFDA-approved in vitro dissolution/permeation methods are available for skin product testing with no specific application to nanocarriers. Researchers are largely utilizing the in-house dissolution/permeation testing methods of nanocarriers. These drug release and permeation methods are pending to be standardized. Their biorelevance with reference to in vivo plasma concentration-time profiles requires further exploration to enable translation of in vitro data for in vivo or clinical performance prediction.
Lipid membranes are extremely stable envelopes allowing cells to survive in various environments and to maintain desired internal composition. Membrane permeation through formation of transversal pores requires substantial external stress. Practically, pores are usually formed by application of lateral tension or transmembrane voltage. Using the same approach as was used for obtaining continuous trajectory of pore formation in the stress-less membrane in the previous article, we now consider the process of pore formation under the external stress. The waiting time to pore formation proved a non-monotonous function of the lateral tension, dropping from infinity at zero tension to a minimum at the tension of several millinewtons per meter. Transmembrane voltage, on the contrary, caused the waiting time to decrease monotonously. Analysis of pore formation trajectories for several lipid species with different spontaneous curvatures and elastic moduli under various external conditions provided instrumental insights into the mechanisms underlying some experimentally observed phenomena.
Asymmetric polyphenylsulfone (PPSU) membranes were fabricated by a non-solvent induced phase inversion method. Glycerin and silica nanoparticles were added into the polymer solution to investigate their effects on the material properties and gas separation performance of prepared membranes. The morphology and structure of PPSU membranes were analyzed by scanning electron microscopy (SEM), the surface roughness of the selective layer was analyzed by atomic force microscopy (AFM), and the surface free energy was calculated based on the contact angle measurements by using various solvents. The gas separation performance of PPSU membranes was estimated by measuring the permeability of CO2 and CH4. The addition of glycerin as a nonsolvent into the polymer solution changed the cross-section structure from finger-like structure into sponge-like structure due to the delayed liquid-liquid demixing process, which was confirmed by SEM analysis. The incorporation of silica nanoparticles into PPSU membranes slightly increased the hydrophilicity, which was confirmed by water contact angle results. PPSU membrane fabricated from the polymer solution containing 10 wt.% glycerin showed the best CO2/CH4 selectivity of 3.86 and the CO2 permeability of 1044.01 Barrer. Mixed matrix PPSU membrane containing 0.1 wt.% silica nanoparticles showed the CO2/CH4 selectivity of 3.16 and the CO2 permeability of 1202.77 Barrer.
The results of many previous studies on low salinity/controlled ions water (CIW) flooding suggest that future laboratory and modeling investigations are required to comprehensively understand and interpret the achieved observations. In this work, the aim is co-optimization of the length of the injected slug and soaking time in the CIW flooding process. Furthermore, the possibility of the occurrence of several governing mechanisms is studied. Therefore, the experimental results were utilized to develop a compositional model, using CMG GEM software, in order to obtain the relative permeability curves by history matching. It was concluded that CIW slug injection, concentrated in the potential-determining ion, can increase oil recovery under a multi ion exchange (MIE) mechanism. The wettability of the carbonate rocks was changed from a mixed or oil wet state toward more water wetness. However, there is a CIW slug length, beyond which extending the length does not significantly improve the rock wettability, and consequently, the oil production, which is known as the optimum slug size. This implies that the optimization of the injection process, by minimizing the slug size, can decrease the need for the CIW supply, therefore lowering the process expenditure. Moreover, if the exposure time of the rock and CIW is increased (soaking), a higher level of ion substitution is probable, leading to more oil detachment and production. Rock dissolution/precipitation (leading to a pH change) was found to have a negligible contribution.