Liposomes as tools for elucidating the mechanisms of membrane fusion
; Liposomes as Tools in Basic Research and Industry (1994); 2017; pp. 103-136. Publisher's VersionAbstract
Membrane fusion is a central biophysical and biochemical reaction in numerous biological processes. Exocytosis involves the fusion of the secretory vesicle membrane with the plasma membrane in diverse biological systems, including neurotransmitter release at the neuromuscular junction, histamine release from mast cells, chromaffin granule extrusion from adrenal medullary cells, trichocyst discharge in Paramecium, endotoxin-induced degranulation in Limulus amebocytes, and the cortical reaction in sea urchin eggs.1-4 The first stage in the formation of an endocytotic vesicle is the fusion of apposed regions of the invaginated plasma membrane. Later in the endocytotic pathway, endosomes and phagosomes fuse with lysosomes. Receptor recycling back to the plasma membrane proceeds through pinching off of receptor-containing vesicles from the compartment of uncoupling of receptor and ligand. Transport of newly synthesized membrane or secretory proteins from the endoplasmic reticulum to the Golgi apparatus, within the cis, medial and trans regions of the Golgi is thought to be mediated by transport vesicles that bud off from one compartment and fuse with another.5-7. © 1995 by Taylor & Francis.
Removal of cyanobacteria and cyanotoxins from lake water by composites of bentonite with micelles of the cation octadecyltrimethyl ammonium (ODTMA)
. Water Research 2017
, 165-173. Publisher's VersionAbstract
Cyanobacteria and their toxins present potential hazard to consumers of water from lakes, reservoirs and rivers, thus their removal via water treatment is essential. The capacity of nano-composites of Octadecyltrimethyl-ammonium (ODTMA) complexed with clay to remove cyanobacterial and their toxins from laboratory cultures and from lake water, was evaluated. Column filters packed with micelles of ODTMA complexed with bentonite and granulated were shown to significantly reduce the number of cyanobacteria cells or filaments and their corresponding toxins from laboratory cultures. Fluorescence measurements demonstrated that cyanobacteria cells lost their metabolic activity (photosynthesis) upon exposure to the micelle (ODTMA)–bentonite complex, or ODTMA monomers. The complex efficiently removed cyanobacteria toxins with an exceptional high removal rate of microcystins. The effectiveness of the complex in elimination of cyanobacteria was further demonstrated with lake water containing cyanobacteria and other phytoplankton species. These results and model calculations suggest that filters packed with granulated composites can secure the safety of drinking water in case of a temporary bloom event of toxic cyanobacteria. © 2017 Elsevier Ltd
Removal of Escherichia coli and total bacteria from water by granulated micelle-clay complexes: Filter regeneration and modeling of filtration kinetics
. Applied Clay Science 2017
, 63-68. Publisher's VersionAbstract
Granulated micelle-clay composites (0.3 to 2 mm) formed from Na-bentonite and the organic cations Octadecyltrimethylammonium (ODTMA), or Benzyldimethylhexadecylammonium (BDMHDA) were employed to remove from water by filtration (a) Escherichia coli S-17 and (b) total bacteria count (TBC). In (a) filters included 4 g to 27 g of complex mixed with sand, and bacteria numbers were 6.4·105 to 5·106/mL. A model which considered convection, adsorption, and desorption simulated the filtration results and yielded predictions. Bacteria capture by filtration was independent of the complex used, but BDMHDA complexes were superior in reducing numbers of emerging bacteria, due to a larger biocidal, or biostatic effect of released cations. Placing a layer of activated carbon after the micelle-clay filter reduced the released cations to 1 μg/L. Regeneration was by: (i) passing a solution of 0.1% NaOCl, or 0.01 M of HCl, or (ii) heating in a furnace at 105 °C for 2.5 h. Capacities for removal of bacteria after first and second regenerations by (i) were 86% and 57% of those with fresh granules, respectively. It is suggested that the technology can provide a safe and economical treatment for drinking water contaminated by pathogenic bacteria. In (b) the capacity of filters was smaller than in (a), but the technology enables to avoid using UV lamps in domestic filters. © 2017 Elsevier B.V.
Comparison of various techniques to estimate the extent and persistence of soil water repellency
. Biologia (Poland) 2017
, 982-987. Publisher's VersionAbstract
New techniques to estimate the extent and persistence of soil water repellency (SWR) were compared with commonly used techniques in assessing the results taken in the long-term agricultural experimental orchards in northern Israel irrigated with either freshwater (FW), primary treated wastewater (WW) or (secondary or tertiary) treated wastewater (TWW), where SWR induced by irrigation was registered (Ha Ma'apil, Neve Etan, and Shafdan). The extent of SWR was assessed by the repellency index RI, combined repellency index RI c and modified repellency index RI m . The persistence of SWR was assessed by the water drop penetration time WDPT and water repellency cessation time WRCT. Soils from different textural classes were classified as slightly to strongly water repellent according to WDPT or RI values. Relationship between RI c and RI values can be well fitted by the linear equation, i.e., RI c could be a good substitute for RI. Relationships between WRCT and WDPT values as well as RI m and RI c or RI values cannot be accurately described by the linear equation, i.e., RI m is not a good substitute for RI for the values taken in this study. © 2017 Institute of Botany, Slovak Academy of Sciences 2017.
Composting municipal biosolids in polyethylene sleeves with forced aeration: Process control, air emissions, sanitary and agronomic aspects
. Waste Management 2017
, 32-42. Publisher's VersionAbstract
Composting in polyethylene sleeves with forced aeration may minimize odor emissions, vectors attraction and leachates associated with open windrows. A disadvantage of this technology is the lack of mixing during composting, potentially leading to non-uniform products. In two pilot experiments using biosolids and green waste (1:1; v:v), thermophilic conditions (>45 °C) were maintained for two months, with successful control of oxygen levels and sufficient moisture. Emitted odors declined from 1.5–3.8 × 105 to 5.9 × 103–2.3 × 104 odor units m−3-air in the first 3 weeks of the process, emphasizing the need of odor control primarily during this period. Therefore, composting might be managed in two phases: (i) a closed sleeve for 6–8 weeks during which the odor is treated; (ii) an open pile (odor control is not necessary). Reduction of salmonella, E. coli and coliforms was effective initially, meeting the standards of “Class A” biosolids; however, total and fecal coliforms density increased after opening the second sleeve and exceeded the standard of 1000 most probable number (MPN) per g dry matter. Compost maturity was achieved in the open piles following the two sleeves and the final compost was non-phytotoxic and beneficial as a soil additive. © 2017 Elsevier Ltd
Laboratory-scale production and purification of the iron chelator rhizoferrin: A novel Fe supplier to plants
. Israel Journal of Plant Sciences 2017
, 136-144. Publisher's VersionAbstract
Rhizopus arrhizus was grown in an iron-free nutrient solution growth medium. Mass production of the siderophores was achieved in a short time by continuous growth of the fungi: after the secretion of the siderophores into the growth medium the spent medium was collected and replaced by a fresh medium while the fungus mat was kept in the flask. The medium exchange was repeated several times and the optimal time for the collection of the siderophore was found to be when the fungus was fully developed, usually about 3 days after the exchange. It was found that it is feasible to grow the fungi continuously for five growth periods, after which the fungus culture becomes too old and collapses. The siderophore was isolated and cleaned from the spent medium using a series of columns on an FPLC at room temperature. Additional tests were used to verify the existence of the siderophore in the solution. The concentrations of rhizoferrin in the various fractions was measured using an exchange reaction between the siderophore and that of an added chelate solution (CAS) while employing a series of dilutions of the CAS. For a precise analytical determination of the siderophore rhizoferrin, Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTICR-MS) was used to validated that the siderophore is indeed rhizoferrin which has been structurally identified earlier. © 2017 by Koninklijke Brill NV, Leiden, The Netherlands.
Water quality and daily temperature cycle affect biofilm formation in drip irrigation devices revealed by optical coherence tomography
. Biofouling 2017
, 211-221. Publisher's VersionAbstract
Drip irrigation is a water-saving technology. To date, little is known about how biofilm forms in drippers of irrigation systems. In this study, the internal dripper geometry was recreated in 3-D printed microfluidic devices (MFDs). To mimic the temperature conditions in (semi-) arid areas, experiments were conducted in a temperature controlled box between 20 and 50°C. MFDs were either fed with two different treated wastewater (TWW) or synthetic wastewater. Biofilm formation was monitored non-invasively and in situ by optical coherence tomography (OCT). 3-D OCT datasets reveal the major fouling position and illustrate that biofilm development was influenced by fluid dynamics. Biofilm volumetric coverage of the labyrinth up to 60% did not reduce the discharge rate, whereas a further increase to 80% reduced the discharge rate by 50%. Moreover, the biofilm formation rate was significantly inhibited in daily temperature cycle independent of the cultivation medium used. © 2017 Informa UK Limited, trading as Taylor & Francis Group.
Water repellency reduction using Soil heating in infiltration ponds of a wastewater soil aquifer treatment (SAT)
. Zeitschrift fur Pflanzenernahrung und Bodenkunde 2017
, 142-152. Publisher's VersionAbstract
Reuse of treated wastewater (TWW) for irrigation in agriculture is a common alternative water source in arid regions suffering from fresh water (FW) shortage. Soil aquifer treatment (SAT) is frequently used for advanced TWW purification. Infiltration rates of water through the soil can decrease as a consequence of organic matter (OM) accumulation and the consequent induction of water repellency. In this research, soil heating to high temperatures was examined for its efficiency in OM content reduction and increased infiltration. In a laboratory experiment conducted using a hand burner and a combustion oven, water repellency was found to be reduced following increased heating temperature or heating duration, directly resulting in reduction of OM level. Chemical analysis of OM extracted from the heat treated soils revealed reduction in hydrophobic substances as a consequence of increased temperatures by soil heating and heating duration. In model ponds built to simulate large infiltration basins, OM content was reduced as a result of intensive and moderate soil heating in comparison to the untreated pond. However, no reduction in water repellency and only slight changes in infiltration rate were found as a consequence of soil heating. The differences in results obtained in the laboratory and the field experiments were probably related to the fact that the soil in the field experiment has been continuously reloaded with TWW containing OM. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Combined adsorption and degradation of the off-flavor compound 2-methylisoborneol in sludge derived from a recirculating aquaculture system
, 69 - 77. Publisher's VersionAbstract
Off-flavor in fish poses a serious threat for the aquaculture industry. In the present study, removal of 2-methylisoborneol (MIB), an off-flavor causing compound, was found to be mediated by adsorption and bacterial degradation in sludge derived from an aquaculture system. A numerical model was developed which augmented Langmuir equations of kinetics of adsorption/desorption of MIB with first order degradation kinetics. When laboratory-scale reactors, containing sludge from the aquaculture system, were operated in a recirculating mode, MIB in solution was depleted to undetectable levels within 6 days in reactors with untreated sludge, while its depletion was incomplete in reactors with sterilized sludge. When operated in an open flow mode, removal of MIB was significantly faster in reactors with untreated sludge. Efficient MIB removal was evident under various conditions, including ambient MIB levels, flow velocities and sludge loads. When operated in an open flow mode, the model successfully predicted steady MIB removal rates with time. During steady state conditions, most of the MIB removal was found to be due to microbial degradation of the adsorbed MIB. Findings obtained in this study can be used in the design of reactors for removal of off-flavor compounds from recirculating aquaculture systems.
The moving-boundary approach for modeling gravity-driven stable and unstable flow in soils
. Water Resources Research 2017
, 344-360. Publisher's VersionAbstract
Abstract The Richards equation is unsuccessful at describing gravity-driven unstable flow with nonmonotonic water content distribution. This shortcoming is resolved in the current study by introducing the moving-boundary approach. Following this approach, the flow domain is divided into two subdomains with a sharp change in fluid saturation between them (moving boundary). The upper subdomain consists of water and air, whose relationship varies with space and time following the imposed boundary condition at the soil surface calculated by the Richards equation. The lower subdomain consists of an initially dry soil that remains constant. The location of the boundary between the two subdomains is part of the solution, rendering the problem nonlinear. The moving boundary solution was used after verification to demonstrate the effect of contact angle, soil characteristic curves and incoming flux on the dynamic water-entry pressure of the soil, which depends on the soil's wettability, incoming flux at the soil surface and the wetting front's propagation rate. Lower soil wettability hinders spontaneous invasion of the dry pores and, together with a higher input flux, induces water accumulation behind the wetting front (saturation overshoot). The wetting front starts to propagate once the pressure building up behind it exceeds the dynamic water-entry pressure. To conclude, the physically based novel moving-boundary approach for solving stable and gravity-driven unstable flow in soils was developed and verified. It supports the conjecture that saturation overshoot is a prerequisite for gravity-driven fingering.
High-throughput physiological phenotyping and screening system for the characterization of plant-environment interactions
. Plant J 2017
We present a simple and effective high-throughput experimental platform for simultaneous and continuous monitoring of water relations in the soil-plant-atmosphere continuum of numerous plants under dynamic environmental conditions. This system provides a simultaneously measured, detailed physiological response profile for each plant in the array, over time periods ranging from a few minutes to the entire growing season, under normal, stress and recovery conditions and at any phenological stage. Three probes for each pot in the array and a specially designed algorithm enable detailed water-relations characterization of whole-plant transpiration, biomass gain, stomatal conductance and root flux. They also enable quantitative calculation of the whole plant water-use efficiency and relative water content at high resolution under dynamic soil and atmospheric conditions. The system has no moving parts and can fit into many growing environments. A screening of 65 introgression lines of a wild tomato species (Solanum pennellii) crossed with cultivated tomato (S. lycopersicum), using our system and conventional gas-exchange tools, confirmed the accuracy of the system as well as its diagnostic capabilities. The use of this high-throughput diagnostic screening method is discussed in light of the gaps in our understanding of the genetic regulation of whole-plant performance, particularly under abiotic stress.
Induced heterogeneity of soil water content and chemical properties by treated wastewater irrigation and its reclamation by freshwater irrigation
. Water Resources Research 2017
, 4756-4774. Publisher's VersionAbstract
Abstract The recognition of treated wastewater (TWW) as an alternative water resource is expanding in areas with a shortage of freshwater (FW) resources. Today, most orchards in Israel are irrigated with TWW. While the benefits of using TWW for irrigation are apparent, evidence of its negative effects on soil, trees, and yield is accumulating. This study, performed in a commercial TWW-irrigated citrus orchard in central Israel, examined the effects of (1) soil-wettability decrease due to prolonged TWW irrigation on the spatial and temporal distribution of water content and associated chemical properties in the root zone; (2) the conversion of irrigation in half of the TWW-irrigated research plot to FW (2012) for soil reclamation. Electrical resistivity tomography surveys in the substantially water repellent soils revealed that water flow is occurring along preferential flow paths in both plots, leaving behind a considerably nonuniform water-content distribution. This was despite the gradual relief in soil water repellency measured in the FW plots. Four soil-sampling campaigns (spring and fall, 2014–2016), performed in 0–20 and 20–40 cm layers of the research plot, revealed bimodal gravimetrically measured water-content distribution. The preferential flow led to uneven chemical-property distribution, with substantially high concentrations in the dry spots, and lower concentrations in the wet spots along the preferential flow paths. The average salt and nutrient concentrations, which were initially high in both plots, gradually dispersed with time, as concentrations in the FW plots decreased. Nevertheless, the efficiency of reclaiming TWW soil by FW irrigation appears low.
A combination of stomata deregulation and a distinctive modulation of amino acid metabolism are associated with enhanced tolerance of wheat varieties to transient drought
. Metabolomics 2017
, 138. Publisher's VersionAbstract
Mediterranean winter crops are commonly and increasingly exposed to irregular rainfall and high temperatures, which lead to transient drought events of different degrees, adversely affecting growth and yield. Hence, exploring the diverse degrees of tolerance to drought existing in the crop and the molecular strategies behind it is pivotal for the development of ad hoc breeding programs.
Broadband optical properties of biomass-burning aerosol and identification of brown carbon chromophores
. Journal of Geophysical Research: Atmospheres 2017
, 5441-5456. Publisher's VersionAbstract
Abstract The radiative effects of biomass-burning aerosols on regional and global scales can be substantial. Accurate modeling of the radiative effects of smoke aerosols requires wavelength-dependent measurements and parameterizations of their optical properties in the UV and visible spectral ranges along with improved description of their chemical composition. To address this issue, we used a recently developed approach to retrieve the time- and spectral-dependent optical properties of ambient biomass-burning aerosols from 300 to 650 nm wavelengths during a regional nighttime bonfire festival in Israel. During the biomass burning event, the overall absorption at 400 nm increased by about 2 orders of magnitude, changing the single scattering albedo from a background level of 0.95 to 0.7. Based on the new retrieval method, we provide parameterizations of the wavelength-dependent effective complex refractive index from 350 to 650 nm for freshly emitted and slightly aged biomass-burning aerosols. In addition, PM2.5 filter samples were collected for detailed offline chemical analysis of the water-soluble organics that contribute to light absorption. Nitroaromatics were identified as major organic species responsible for the increased absorption at 400 to 500 nm. Typical chromophores include 4-nitrocatechol, 4-nitrophenol, nitrosyringol, and nitroguaiacol; oxidation-nitration products of methoxyphenols; and known products of lignin pyrolysis. Our findings emphasize the importance of both primary and secondary organic aerosols from biomass burning in absorption of solar radiation and in effective radiative forcing.
Ozone Formation Induced by the Impact of Reactive Bromine and Iodine Species on Photochemistry in a Polluted Marine Environment
. Environmental Science & TechnologyEnvironmental Science & Technology 2017
, 14030 - 14037. Publisher's VersionAbstract
Reactive iodine and bromine species (RIS and RBS, respectively) are known for altering atmospheric chemistry and causing sharp tropospheric ozone (O3) depletion in polar regions and significant O3 reduction in the marine boundary layer (MBL). Here we use measurement-based modeling to show that, unexpectedly, both RIS and RBS can lead to enhanced O3 formation in a polluted marine environment under volatile organic compound (VOC)-limited conditions associated with high nitrogen oxide (NOX = [NO] + [NO2]) concentrations. Under these conditions, the daily average O3 mixing ratio increased to ∼44 and ∼28% for BrO and IO mixing ratios of up to ∼6.8 and 4.7 ppt, respectively. The increase in the level of O3 was partially induced by enhanced ClNO3 formation for higher Br2 and I2 emission flux. The increase in the level of O3 was associated with an increased mixing ratio of hydroperoxyl radical to hydroxyl radical ([HO2]/[OH]) and increased [NO2]/[NO] with higher levels of RBS and/or RIS. NOX-rich conditions are typical of the polluted MBL, near coastlines and ship plumes. Considering that O3 is toxic to humans, plants, and animals and is a greenhouse gas, our findings call for adequate updating of local and regional air-quality models with the effects of activities of RBS and RIS on O3 mixing ratios in the polluted MBL.Reactive iodine and bromine species (RIS and RBS, respectively) are known for altering atmospheric chemistry and causing sharp tropospheric ozone (O3) depletion in polar regions and significant O3 reduction in the marine boundary layer (MBL). Here we use measurement-based modeling to show that, unexpectedly, both RIS and RBS can lead to enhanced O3 formation in a polluted marine environment under volatile organic compound (VOC)-limited conditions associated with high nitrogen oxide (NOX = [NO] + [NO2]) concentrations. Under these conditions, the daily average O3 mixing ratio increased to ∼44 and ∼28% for BrO and IO mixing ratios of up to ∼6.8 and 4.7 ppt, respectively. The increase in the level of O3 was partially induced by enhanced ClNO3 formation for higher Br2 and I2 emission flux. The increase in the level of O3 was associated with an increased mixing ratio of hydroperoxyl radical to hydroxyl radical ([HO2]/[OH]) and increased [NO2]/[NO] with higher levels of RBS and/or RIS. NOX-rich conditions are typical of the polluted MBL, near coastlines and ship plumes. Considering that O3 is toxic to humans, plants, and animals and is a greenhouse gas, our findings call for adequate updating of local and regional air-quality models with the effects of activities of RBS and RIS on O3 mixing ratios in the polluted MBL.
The influence of compost and zeolite co-addition on the nutrients status and plant growth in intensively cultivated Mediterranean soils
. Soil Use and Management 2017
, 72-80. Publisher's VersionAbstract
Abstract The main objective of the study was to test the benefits of compost and zeolite co-addition on the fertility of organic-rich Mediterranean soils. Previous pot study in greenhouse found that zeolites mixed with compost significantly improved potassium availability as well as exchangeable potassium capacity in the soils. To further test this finding, a field experiment was conducted using potato – Solanum tuberosum L., desiree cultivar in peat soils of the Hula Valley, Israel. Adhering to the protocol of the greenhouse experiments, the treatments included 5% compost addition with no zeolites, 2% zeolite addition without compost, co-addition of 5% compost mixed with 2% zeolites and control. We found that compost addition increased significantly the potatoes yield and the number of large tubers; however, the zeolite addition had no impact on yield. Co-addition of compost and zeolites did not improve total crop yield or number of large tubers compared with compost addition only. The results are consistent with nutrients availability (N, P, K) across the treatments. In a commercialized field using the experiment conditions, the 2% zeolite addition would amount to 18 ton of zeolites per hectare. Hence, we conclude that soil amendment with the tested zeolite might be beneficial to improve soil retention for cationic nutrients (e.g. K+) under high leaching systems such as plant culture in pots, but in the field with high loads of compost, its effect is minor.
Catalytic polymer-clay composite for enhanced removal and degradation of diazinon
. J Hazard Mater 2017
It is well established that organophosphate pesticides, such as diazinon, pose environmental and health risks. Diazinon is prone to rapid acidic hydrolysis, forming the less toxic compound 2-isopropyl-6-methyl-4-pyrimidinol (IMP). In this study, diazinon surface catalyzed hydrolysis was achieved by its adsorption to a composite, based on protonated poly (4-vinyl-pyridine-co-styrene) (HPVPcoS) and montmorillonite (MMT) clay. The adsorption affinity and kinetics of diazinon to HPVPcoS-MMT were significantly higher than those obtained to the deprotonated PVPcoS-MMT, emphasizing the importance of hydrogen bonding. Correspondingly, diazinon filtration by HPVPcoS-MMT columns was highly efficient (100% for 100 pore volumes), while filtration by columns of PVPcoS-MMT or granular activated carbon (GAC) reached only 55% and 85%, respectively. Regeneration of HPVPcoS-MMT by pH increase was demonstrated and sorbent reuse was successful, whereas regeneration and reuse of GAC and PVPcoS-MMT were inefficient. Proton transfer from HPVPcos-MMT to diazinon, investigated by FTIR analysis, supports the suggested mechanism of surface catalyzed hydrolysis. These findings demonstrate the applicability of such bi-functional sorbents, to adsorb and degrade pollutants, for efficient water treatment.
Pairing micropollutants and clay-composite sorbents for efficient water treatment: Filtration and modeling at a pilot scale
. Applied Clay Science 2017
, 225 - 232. Publisher's VersionAbstract
Organically modified clay minerals have been widely developed, tested and employed as sorbents for organic pollutants. However, the process of pollutant-composite pairing is not commonly addressed, which would be valuable for efficient pollutant filtration by such sorbents. This study presents an approach for achieving efficient pollutant removal by large-scale composite filters, based on pairing chemically compatible pollutants and composites and by employing a predictive filtration model. The removal of three organic pollutants, simazine, sulfentrazone and diclofenac by lab-scale filtration columns containing one of three sorbents, a polymer-, micelle- or liposome-clay composite, was measured. Understanding the factors governing pollutant-organic modifier interactions enabled to pair an efficient sorbent to each pollutant. The high removal (80%) of simazine by the polymer composite, was attributed to hydrogen bonds and π-π interactions, compared to less than 20% removal by the surfactant composites. The removal of the anionic diclofenac (pKa=4.1) was mainly governed by electrostatic attraction, explaining its high removal by the most positively charge sorbent, the liposome composite. Sulfentrazone (pKa=6.5) removal was mostly affected by micellar solubilization and upon its removal, the zeta potential of the micelle-composite was not reduced as obtained for diclofenac removal. The filtration of the successful pairs was modelled to determine sorbent capacity and adsorption and desorption rate constants. The pilot filtration experiments were well described by the model and demonstrated efficient removal of paired pollutants and sorbents. Model simulations predicted promising treatment at environmental pollutant concentrations in the μgL−1 range. This pairing approach along with model calculations can be a strong and valid tool for efficient pollutant-sorbent filtration.
PEG-PE/clay composite carriers for doxorubicin: Effect of composite structure on release, cell interaction and cytotoxicity
. Acta Biomater 2017
A novel drug delivery system for doxorubicin (DOX), based on organic-inorganic composites was developed. DOX was incorporated in micelles (M-DOX) of polyethylene glycol-phosphatidylethanolamine (PEG-PE) which in turn were adsorbed by the clay, montmorillonite (MMT). The nano-structures of the PEG-PE/MMT composites of LOW and HIGH polymer loadings were characterized by XRD, TGA, FTIR, size (DLS) and zeta measurements. These measurements suggest that for the LOW composite a single layer of polymer intercalates in the clay platelets and the polymer only partially covers the external surface, while for the HIGH composite two layers of polymer intercalate and a bilayer may form on the external surface. These nanostructures have a direct effect on formulation stability and on the rate of DOX release. The release rate was reversely correlated with the degree of DOX interaction with the clay and followed the sequence: M-DOX>HIGH formulation>LOW formulation>DOX/MMT. Despite the slower release from the HIGH formulation, its cytotoxicity effect on sensitive cells was as high as the "free" DOX. Surprisingly, the LOW formulation, with the slowest release, demonstrated the highest cytotoxicity in the case of Adriamycin (ADR) resistant cells. Confocal microscopy images and association tests provided an insight into the contribution of formulation-cell interactions vs. the contribution of DOX release rate. Internalization of the formulations was suggested as a mechanism that increases DOX efficiency, particularly in the ADR resistant cell line. The employment of organic-inorganic hybrid materials as drug delivery systems, has not reached its full potential, however, its functionality as an efficient tunable release system was demonstrated. STATEMENT OF SIGNIFICANCE: DOX PEG-PE/clay formulations were design as an efficient drug delivery system. The main aim was to develop PEG-PE/clay formulations of different structures based on various PEG-PE/clay ratios in order to achieve tunable release rates, to control the external surface characteristics and formulation stability. The formulations showed significantly higher toxicity in comparison to "free" DOX, explained by formulation internalization. For each cell line tested, sensitive and ADR resistant, a different formulation structure was found most efficient. The potential of PEG-PE/clay-DOX formulations to improve DOX administration efficacy was demonstrated and should be further explored and implemented for other cancer drugs and cells.