Effect of a Ketogenic Diet on Oxidative Posttranslational Protein Modifications and Brain Homogenate Denaturation in the Kindling Model of Epilepsy in Mice.

This study focused on the ketogenic diet (KD) effects on oxidative posttranslational protein modification (PPM) as presumptive factors implicated in epileptogenesis. A 28-day of KD treatment was performed. The corneal kindling model of epileptogenesis was used. Four groups of adult male ICR mice (25-30 g) were randomized in standard rodent chow (SRC) group, KD-treatment group; SRC + kindling group; KD + kindling group (n = 10 each). Advanced oxidation protein products (AOPP) and protein carbonyl contents of brain homogenates together with differential scanning calorimetry (DSC) were evaluated. Two exothermic transitions (Exo1 and Exo2) were explored after deconvolution of the thermograms. Factor analysis was applied. The protective effect of KD in the kindling model was demonstrated with both decreased seizure score and increased seizure latency. KD significantly decreased glucose and increased ketone bodies (KB) in blood. Despite its antiseizure effect, the KD increased the AOPP level and the brain proteome's exothermic transitions, suggestive for qualitative modifications. The ratio of the two exothermic peaks (Exo2/Exo1) of the thermograms from the KD vs. SRC treated group differed more than twice (3.7 vs. 1.6). Kindling introduced the opposite effect, changing this ratio to 2.7 for the KD + kindling group. Kindling significantly increased glucose and KB in the blood whereas decreased the BW under the SRC treatment. Kindling decreased carbonyl proteins in the brain irrespectively of the diet. Further evaluations are needed to assess the nature of correspondence of calorimetric images of the brain homogenates with PPM.

The effect of prolonged intense physical exercise of special forces volunteers on their plasma protein denaturation profile examined by differential scanning calorimetry.

The human blood plasma proteome profile has been an area of intensive investigation and differential scanning calorimetry (DSC) has come forward as a novel tool in analyzing plasma heat capacity changes to monitor various physiological responses in health and disease. This study used DSC to assess potential alterations in the plasma heat capacity profile of albumin and globulins during extremely demanding physical exercise. We monitored the changes in denaturation profiles of those plasma proteins for five consecutive days of an extraordinary exercise training schedule in 14 young male Special Forces volunteers, as well as after a 30-day recovery period. The major effect of the prolonged intense exercise was the continuous upward shift of the albumin peak by 2°-3 °C on the initial days of exercise, with a tendency to plateau circa the 5th day of exercise. In addition, some redistribution of the denaturational enthalpy was observed upon exercise, where the globulins peak increased relative to the albumin peak. Noteworthy, the alterations in the plasma proteome denaturational profiles were not persistent, as virtually full recovery of the initial status was observed after 30 days of recovery. Our findings indicate that 5 days of exhaustive physical exercise of highly trained individuals enhanced the thermal stability of plasma albumin shifting its denaturational transition to higher temperatures. We surmise that these effects may be a result of increased blood oxygenation during the prolonged intense exercise and, consequently, of albumin oxidation as part of the overall adaptation mechanisms of the body to extreme physical and/or oxidative stress.

Exothermic transitions in the heat capacity profiles of human cerebrospinal fluid.

In this work, we examined by DSC protein denaturation heat capacity profiles for two body fluids, cerebrospinal fluid (CSF) and blood plasma obtained from brain tumor (mainly glioblastoma) patients and healthy volunteers. We observed large distinctions between the heat capacity profiles of CSF and blood plasma, although their protein compositions are believed to have much in common. A prominent, previously unreported CSF feature was the existence of a pre-denaturation exothermic transition peaking at ~ 50-52 °C, recorded for both control and brain tumor CSF. This appears to be the first observation of a pre-denaturation exotherm in a human body fluid. In all studied samples, the exotherms deconvoluted with high precision into a sum of two Gaussian peaks. These exotherms are apparently specific, originating from brain tissue-soluble proteins in the CSF not present in blood plasma. Malignant brain tumors (glioblastoma multiforme, Grade IV, and low-grade glioma, Grade II) reduced twofold the enthalpy of the exotherms relative to the control. These results suggest that the amount and/or conformational state of the CSF proteins (e.g., intrinsic disorder) giving rise to pre-denaturation exothermic events substantially changed upon brain tumor progression. Concomitantly, the enthalpy of the CSF endothermic peaks was partially redistributed from a lower-temperature (main) transition to a higher-temperature transition. The presented data demonstrated that the heat capacity profiles of intrinsic CSF proteins constitute a sensitive biomarker of glioblastoma and other brain malignancies.

A novel DSC approach for evaluating protectant drugs efficacy against dementia.

Differential scanning calorimetry was applied to evaluate the efficacy of preventive treatments with biologically active compounds of plant origin against neurodegenerative disorder in mice. As we reported recently, large differences exist between the heat capacity profiles of water-soluble brain proteome fractions from healthy animals and from animals with scopolamine-induced dementia: the profiles for healthy animals displayed well expressed exothermic event peaking at 40-45°C, by few degrees above body temperature, but still preceding in temperature the proteome endothermic denaturational transitions; the low-temperature exotherm was completely abolished by the scopolamine treatment. Here we explored this signature difference in the heat capacity profiles to assess the efficacy of preventive treatments with protectant drugs anticipated to slow down or block progression of dementia (myrtenal, ellagic acid, lipoic acid and their combinations, including also ascorbic acid). We found that these neuroprotectants counteract the scopolamine effect and partially or completely preserve the 'healthy' thermogram, and specifically the low-temperature exotherm. These results well correlate with the changes in the cognitive functions of the animals assessed using the Step Through Test for learning and memory. The exothermic event is deemed to be associated with a reversible process of fibrillization and/or aggregation of specific water-soluble brain protein fractions preceding their denaturation. Most importantly, the results demonstrate that the effect of scopolamine and its prevention by protectant substances are clearly displayed in the heat capacity profiles of the brain proteome, thus identifying DSC as a powerful method in drug testing and discovery.

Cubic phases in membrane lipids.

On the basis of data obtained by time-resolved X-ray diffraction, we consider in the present article the occurrence and formation pathways of inverted bicontinuous cubic phases, or bilayer cubic phases, Q (II)(B) , in diluted dispersions of lipids representing major biomembrane lipid classes [phosphatidylethanolamines (PEs), mixtures of PEs and phosphatidylcholines (PCs) with other lipids, glycolipids]. We show that Q (II)(B) formation proceeds much more easily upon cooling from the H(II) phase than upon heating or isothermal conversion from the L(α) phase, thus identifying an indirect but faster route for Q (II)(B) phase induction in lipids. The data collected consistently show that the ability to convert into cubic phase upon temperature cycling appears to be a general property of all lipids exhibiting an L(α) ↔ H(II) phase transition. Admixtures of charged phospholipids, both anionic and cationic, strongly facilitate Q (II)(B) formation in PEs. Their effect may be attributed to increased electrostatic repulsion between the lipid bilayers that reduces the unbinding energy and facilitates the dissipation of the L(α) phase required for its conversion into bilayer cubic phase.

Nanosized self-emulsifying lipid vesicles of diacylglycerol-PEG lipid conjugates: biophysical characterization and inclusion of lipophilic dietary supplements.

Hydrated diacylglycerol-PEG lipid conjugates, glyceryl dioleate-PEG12 (GDO-PEG12) and glyceryl dipalmitate-PEG23 (GDP-PEG23), spontaneously form uni- or oligolamellar liposomes in their liquid crystalline phase, in distinct difference from the PEGylated phospholipids which form micelles. GDP-PEG23 exhibits peculiar hysteretic phase behavior and can arrange into a long-living hexagonal phase at ambient and physiological temperatures. Liposomes of GDO-PEG12 and its mixture with soy lecithin exchange lipids with the membranes much more actively than common lecithin liposomes; such an active lipid exchange might facilitate the discharging of the liposome cargo upon uptake and internalization, and can thus be important in drug delivery applications. Diacylglycerol-PEG lipid liposome formulations can encapsulate up to 20-30wt.% lipophilic dietary supplements such as fish oil, coenzyme Q10, and vitamins D and E. The encapsulation is feasible by way of dry mixing, avoiding the use of organic solvent.

Bilayer structural destabilization by low amounts of chlorophyll a.

The present study shows that small admixtures of one chlorophyll a (Chla) molecule per several hundred lipid molecules have strong destabilizing effect on lipid bilayers. This effect is clearly displayed in the properties of the L(alpha)-H(II) transformations and results from a Chla preference for the H(II) relative to the L(alpha) phase. Chla disfavors the lamellar liquid crystalline phase L(alpha) and induces its replacement with inverted hexagonal phase H(II), as is consistently demonstrated by DSC and X-ray diffraction measurements on phosphatidylethanolamine (PE) dispersions. Chla lowers the L(alpha)-H(II) transition temperature (42 degrees C) of the fully hydrated dipalmitoleoyl PE (DPoPE) by approximately 8 degrees C and approximately 17 degrees C at Chla/DPoPE molar ratios of 1:500 and 1:100, respectively. Similar Chla effect was recorded also for dielaidoyl PE dispersions. The lowering of the transition temperature and the accompanying significant loss of transition cooperativity reflect the Chla repartitioning and preference for the H(II) phase. The reduction of the H(II) phase lattice constant in the presence of Chla is an indication that Chla favors H(II) phase formation by decreasing the radius of spontaneous monolayer curvature, and not by filling up the interstitial spaces between the H(II) phase cylinders. The observed Chla preference for H(II) phase and the substantial bilayer destabilization in the vicinity of a bilayer-to-nonbilayer phase transformation caused by low Chla concentrations can be of interest as a potential regulatory or membrane-damaging factor.

Cationic lipids: molecular structure/ transfection activity relationships and interactions with biomembranes.

Abstract Synthetic cationic lipids, which form complexes (lipoplexes) with polyanionic DNA, are presently the most widely used constituents of nonviral gene carriers. A large number of cationic amphiphiles have been synthesized and tested in transfection studies. However, due to the complexity of the transfection pathway, no general schemes have emerged for correlating the cationic lipid chemistry with their transfection efficacy and the approaches for optimizing their molecular structures are still largely empirical. Here we summarize data on the relationships between transfection activity and cationic lipid molecular structure and demonstrate that the transfection activity depends in a systematic way on the lipid hydrocarbon chain structure. A number of examples, including a large series of cationic phosphatidylcholine derivatives, show that optimum transfection is displayed by lipids with chain length of approximately 14 carbon atoms and that the transfection efficiency strongly increases with increase of chain unsaturation, specifically upon replacement of saturated with monounsaturated chains.

Modulation of a membrane lipid lamellar-nonlamellar phase transition by cationic lipids: a measure for transfection efficiency.

Synthetic cationic lipids can be used as DNA carriers and are regarded to be the most promising non-viral gene carriers. For this investigation, six novel phosphatidylcholine (PC) cationic derivatives with various hydrophobic moieties were synthesized and their transfection efficiencies for human umbilical artery endothelial cells (HUAEC) were determined. Three compounds with relatively short, myristoleoyl or myristelaidoyl 14:1 chains exhibited very high activity, exceeding by approximately 10 times that of the reference cationic derivative dioleoyl ethylPC (EDOPC). Noteworthy, cationic lipids with 14:1 hydrocarbon chains have not been tested as DNA carriers in transfection assays previously. The other three lipids, which contained oleoyl 18:1 and longer chains, exhibited moderate to weak transfection activity. Transfection efficiency was found to correlate strongly with the effect of the cationic lipids on the lamellar-to-inverted hexagonal, Lalpha-->HII, phase conversion in dipalmitoleoyl phosphatidylethanolamine dispersions (DPoPE). X-ray diffraction on binary DPoPE/cationic lipid mixtures showed that the superior transfection agents eliminated the direct Lalpha-->HII phase transition and promoted formation of an inverted cubic phase between the Lalpha and HII phases. In contrast, moderate and weak transfection agents retained the direct Lalpha-->HII transition but shifted to higher temperatures than that of pure DPoPE, and induced cubic phase formation at a later stage. On the basis of current models of lipid membrane fusion, promotion of a cubic phase by the high-efficiency agents may be considered as an indication that their high transfection activity results from enhanced lipoplex fusion with cellular membranes. The distinct, well-expressed correlation established between transfection efficiency of a cationic lipid and the way it modulates nonlamellar phase formation of a membrane lipid could be useful as a criterion to assess the quality of lipid carriers and for rational design of new and superior nucleotide delivery agents.

Natural lipid extracts and biomembrane-mimicking lipid compositions are disposed to form nonlamellar phases, and they release DNA from lipoplexes most efficiently.

A viewpoint now emerging is that a critical factor in lipid-mediated transfection (lipofection) is the structural evolution of lipoplexes upon interacting and mixing with cellular lipids. Here we report our finding that lipid mixtures mimicking biomembrane lipid compositions are superior to pure anionic liposomes in their ability to release DNA from lipoplexes (cationic lipid/DNA complexes), even though they have a much lower negative charge density (and thus lower capacity to neutralize the positive charge of the lipoplex lipids). Flow fluorometry revealed that the portion of DNA released after a 30-min incubation of the cationic O-ethylphosphatidylcholine lipoplexes with the anionic phosphatidylserine or phosphatidylglycerol was 19% and 37%, respectively, whereas a mixture mimicking biomembranes (MM: phosphatidylcholine/phosphatidylethanolamine/phosphatidylserine /cholesterol 45:20:20:15 w/w) and polar lipid extract from bovine liver released 62% and 74%, respectively, of the DNA content. A possible reason for this superior power in releasing DNA by the natural lipid mixtures was suggested by structural experiments: while pure anionic lipids typically form lamellae, the natural lipid mixtures exhibited a surprising predilection to form nonlamellar phases. Thus, the MM mixture arranged into lamellar arrays at physiological temperature, but began to convert to the hexagonal phase at a slightly higher temperature, approximately 40-45 degrees C. A propensity to form nonlamellar phases (hexagonal, cubic, micellar) at close to physiological temperatures was also found with the lipid extracts from natural tissues (from bovine liver, brain, and heart). This result reveals that electrostatic interactions are only one of the factors involved in lipid-mediated DNA delivery. The tendency of lipid bilayers to form nonlamellar phases has been described in terms of bilayer "frustration" which imposes a nonzero intrinsic curvature of the two opposing monolayers. Because the stored curvature elastic energy in a "frustrated" bilayer seems to be comparable to the binding energy between cationic lipid and DNA, the balance between these two energies could play a significant role in the lipoplex-membrane interactions and DNA release energetics.

Lipoplex formulation of superior efficacy exhibits high surface activity and fusogenicity, and readily releases DNA.

Lipoplexes containing a mixture of cationic phospholipids dioleoylethylphosphatidylcholine (EDOPC) and dilauroylethylphosphatidylcholine (EDLPC) are known to be far more efficient agents in transfection of cultured primary endothelial cells than are lipoplexes containing either lipid alone. The large magnitude of the synergy permits comparison of the physical and physico-chemical properties of lipoplexes that have very different transfection efficiencies, but minor chemical differences. Here we report that the superior transfection efficiency of the EDLPC/EDOPC lipoplexes correlates with higher surface activity, higher affinity to interact and mix with negatively charged membrane-mimicking liposomes, and with considerably more efficient DNA release relative to the EDOPC lipoplexes. Observations on cultured cells agree with the results obtained with model systems; confocal microscopy of transfected human umbilical artery endothelial cells (HUAEC) demonstrated more extensive DNA release into the cytoplasm and nucleoplasm for the EDLPC/EDOPC lipoplexes than for EDOPC lipoplexes; electron microscopy of cells fixed and embedded directly on the culture dish revealed contact of EDLPC/EDOPC lipoplexes with various cellular membranes, including those of the endoplasmic reticulum, mitochondria and nucleus. The sequence of events outlining efficient lipofection is discussed based on the presented data.

Natural Product Formulations for the Prevention and Treatment of Alzheimer's disease: A Patent Review.

INTRODUCTION: Although considerable efforts have been made to develop effective therapeutic agents for Alzheimer's Disease (AD), neither a consensus concerning the pathogenesis of the disease nor a successful therapy for its treatment is yet available. The natural product chemistry brings tremendous diversity and abundant resource for medical needs. OBJECTIVES: The present review summarizes recent patents on natural extracts and derived drugs as agents for the prevention and treatment of AD. It also sums up the suggested mechanisms of action of the formulated natural remedies. CONCLUSION: It is now becoming well accepted that multiple factors contribute to the progression of AD. The pathogenesis of the disease involves amyloid-ß cascade, tau hyperphosphorylation, oxidative stress, inflammation, mitochondrial dysfunction, protein misfolding, gene mutation, etc. It has been suggested that the multifactorial nature of AD pathogenesis requires the design of medicines with a wide spectrum of activity. Medicinal herbs are known to consist of multiple compounds and may implicate multiple mechanisms, thus being advantageous over the simple single-target drugs in the treatment of complex diseases. Indeed, natural products attract increased attention. In the last decades, they have become a major focus in the quest for AD remedies and may represent a real promise for curing the disease.

Calorimetric monitoring data of the evolution of the lamellar-inverted hexagonal phase transition in phosphatidylethanolamine dispersions upon temperature cycling.

The data presented in this article are related to the research article entitled "Cubic phases in phosphatidylethanolamine dispersions: formation, stability and phase transitions" (Tenchov and Koynova, 2017) [1]. This article presents thermodynamic data obtained by differential scanning calorimetry following the evolution of the Lα - HII endotherm upon temperature cycling during the lamellar to cubic phase conversion.

Synergy in lipofection by cationic lipid mixtures: superior activity at the gel-liquid crystalline phase transition.

Some mixtures of two cationic lipids including phospholipid compounds (O-ethylphosphatidylcholines) as well as common, commercially available cationic lipids, such as dimethylammonium bromides and trimethylammonium propanes, deliver therapeutic DNA considerably more efficiently than do the separate molecules. In an effort to rationalize this widespread "mixture synergism", we examined the phase behavior of the cationic lipid mixtures and constructed their binary phase diagrams. Among a group of more than 50 formulations, the compositions with maximum delivery activity resided unambiguously in the solid-liquid crystalline two-phase region at physiological temperature. Thus, the transfection efficacy of formulations exhibiting solid-liquid crystalline phase coexistence is more than 5 times higher than that of formulations in the gel (solid) phase and over twice that of liquid crystalline formulations; phase coexistence occurring at physiological temperature thus appears to contribute significantly to mixture synergism. This relationship between delivery activity and physical property can be rationalized on the basis of the known consequences of lipid-phase transitions, namely, the accumulation of defects and increased disorder at solid-liquid crystalline phase boundaries. Packing defects at the borders of coexisting solid and liquid crystalline domains, as well as large local density fluctuations, could be responsible for the enhanced fusogenicity of mixtures. This study leads to the important conclusion that manipulating the composition of the lipid carriers so that their phase transition takes place at physiological temperature can enhance their delivery efficacy.

Cubic phases in phosphatidylethanolamine dispersions: Formation, stability and phase transitions.

The non-lamellar phases formed by membrane lipids in diluted aqueous dispersions are mainly represented by the inverted hexagonal phase, HII, and phases of cubic symmetry, among them the bicontinuous cubic phases Pn3m (Q224), Im3m (Q229) and Ia3d (Q230). Here we report X-ray diffraction data on phosphatidylethanolamine (PE) dispersions forming highly stable Im3m and Pn3m cubic phases at ambient temperature as a result of a temperature cycling through the Lα - HII transition and complement the structural characterization of the PE phase transitions with thermodynamic data obtained by differential scanning calorimetry and differential scanning densitometry. All studied PEs displayed irreversible two-state Im3m → Pn3m phase transitions in the range ∼75-85°C with enthalpy of ∼100cal/mol. By contrast with the Lα - HII transition, the Im3m → Pn3m transition was not accompanied by a stepwise change of the specific volume. The cubic phases induced in dipalmitoleoyl PE dispersions are of particular interest because of their facile formation, especially in the presence of small amounts of charged lipid admixtures, and long-term stability at physiologically relevant conditions in a broad temperature range around room temperature.

Lipid transfer between cationic vesicles and lipid-DNA lipoplexes: effect of serum.

Differential scanning calorimetry was used to examine the lipid exchange between model lipid systems, including vesicles of the cationic lipoids ethyldimyristoylphosphatidylcholine (EDMPC), ethyldipalmitoylphosphatidylcholine (EDPPC) or their complexes with DNA (lipoplexes), and the zwitterionic lipids (DMPC, DPPC). The changes of the lipid phase transition parameters (temperature, enthalpy, and cooperativity) upon consecutive temperature scans was used as an indication of lipid mixing between aggregates. A selective lipid transfer of the shorter-chain cationic lipoid EDMPC into the longer-chain aggregates was inferred. In contrast, transfer was hindered when EDMPC (but not EDPPC) was bound to DNA in the lipoplexes. These data support a simple molecular lipid exchange mechanism, but not lipid bilayer fusion. Exchange via lipid monomers is considerably more facile for the cationic ethylphosphatidylcholines than for zwitterionic phosphatidylcholines, presumably due to the higher monomer solubility of the charged lipids. With the cationic liposomes, lipid transfer was strongly promoted by the presence of serum in the dispersing medium. Serum proteins are presumed to be responsible for the accelerated transfer, since the effect was strongly reduced upon heating the serum to 80 degrees C. The effect of serum indicates that even though much lipoplex lipid is inaccessible due to the multilayered structure, the barrier due to buried lipid can be easily overcome. Serum did not noticeably promote the lipid exchange of zwitterionic liposomes. The phenomenon is of potential importance for the application of cationic liposomes to nonviral gene delivery, which often involves the presence of serum in vitro, and necessarily involves serum contact in vivo.

Cationic O-ethylphosphatidylcholines and their lipoplexes: phase behavior aspects, structural organization and morphology.

Ethylphosphatidylcholines, positively charged membrane lipid derivatives in which the anionic charge of the phosphate oxygen has been eliminated by ethylation, are promising nonviral, metabolizable transfection agents. We studied in detail the phase behavior, structural organization and morphology of the ethylphosphatidylcholines and their lipoplexes. Unlike the other phospholipids, dehydration does not change the melting transition temperature of O-ethyl-dipalmitoylphosphatidylcholine (EDPPC). Neither does an isoelectric amount of DNA, when added to the EDPPC aqueous dispersion. This is ascribed to the inability of EDPPC to form hydrogen bonds because of its headgroup modification. Similarly to its parent lipid DPPC, EDPPC displays a subtransition at 15 degrees C in its differential scanning calorimetry (DSC) heating scans after prolonged low-temperature incubation. The cooling behavior of the O-ethylphosphatidylcholines is sensitive to the thermal prehistory and the ionic strength. Different aggregate morphologies in the solid and the liquid-crystalline phases-respectively lamellar sheets and vesicles, as documented by light microscopy-are considered responsible for the cooling pattern. The interconversion between these morphologies is slow or even kinetically hindered, however, increasing the ionic strength to physiological values facilitates the conversion. The interdigitated chain arrangement of EDPPC gel phase tolerates incorporation of DNA between the bilayers. The minimum observed separation between the DNA strands is approximately 30-32 A, at DNA/lipid molar ratio > or =1. Formation of lipoplexes with DNA ordered in a 1-D lattice sandwiched between interdigitated lipid bilayers is reported for the first time.

Recent Progress in Liposome Production, Relevance to Drug Delivery and Nanomedicine.

From their discovery half a century ago and the subsequent appreciation of their clinical utility, liposomes currently hold a recognized position in the mainstream of drug delivery systems. Conventional techniques for liposome preparation and size reduction are simple to implement and do not require sophisticated equipment. However, most of them are not easy to scale-up for industrial liposome production. With several liposomal formulations already on the market, and more in final clinical trials, the industrial scale production of liposomes has become reality, and so the range of liposome preparation methods has been extended by a number of techniques which are increasingly attractive, such as microfluidic hydrodynamic focusing, supercritical fluid processing, freeze-drying and spray-drying. Some of these new techniques generally represent advancements of the conventional methods allowing for scale-up, better reproducibility and process control. This review summarizes patents in the last decade offering new techniques for production of liposomes as related to their application in drug delivery.

Nonlamellar Phases in Cationic Phospholipids, Relevance to Drug and Gene Delivery.

Lipid aggregates have been used as drug carriers for several decades. Recently, nonlamellar liquid crystalline lipid systems have attracted attention as possible drug-delivery vehicles because of their unique nanostructure and physicochemical properties. Here we summarize data on the nonlamellar phase-forming propensity of the cationic phosphatidylcholines (cationic PCs). The class of cationic PCs has been specifically designed and explored for the purpose of nonviral gene delivery. These lipids were found to comprise an attractive cationic lipid class because they are biodegradable, have low toxicities, and in a number of cases, display high transfection activity. Lipids of this class form a variety of polymorphic and mesomorphic phases-lamellar and nonlamellar, depending on the structure of their hydrocarbon chains and especially on the third hydrocarbon chain used to alkylate the PC phosphate group and convert the zwitterionic PC headgroup into a cation. Here we characterize the phase behavior and transfection activity of eight cationic PCs that have been identified as forming nonlamellar phases-inverted hexagonal and cubic. We then demonstrate that those cationic PCs that also form nonlamellar lipoplexes are notably less efficient gene nanocarriers in comparison with the cationic PCs forming lamellar phase lipoplexes.

An index of lipid phase diagrams.

There is a growing awareness of the utility of lipid phase behavior data in studies of membrane-related phenomena. Such miscibility information is commonly reported in the form of temperature-composition (T-C) phase diagrams. The current index is a conduit to the relevant literature. It lists lipid phase diagrams, their components and conditions of measurement, and complete bibliographic information. The main focus of the index is on lipids of membrane origin where water is the dispersing medium. However, it also includes records on acylglycerols, fatty acids, cationic lipids, and detergent-containing systems. The miscibility of synthetic and natural lipids with other lipids, with water, and with biomolecules (proteins, nucleic acids, carbohydrates, etc.) and non-biological materials (drugs, anesthetics, organic solvents, etc.) is within the purview of the index. There are 2188 phase diagram records in the index, the bulk (81%) of which refers to binary (two-component) T-C phase diagrams. The remainder is made up of more complex (ternary, quaternary) systems, pressure-T phase diagrams, and other more exotic miscibility studies. The index covers the period from 1965 through to July, 2001.