Phospholipid Bilayer Of Liposomes Research Articles

Molecular Dynamics Simulations Reveal Octanoylated Hyaluronic Acid Enhances Liposome Stability, Stealth and Targeting.

Liposome-based drug delivery systems have been widely used in drug and gene delivery. However, issues such as instability, immune clearance, and poor targeting have significantly limited their clinical utility. Consequently, there is an urgent need for innovative strategies to improve liposome performance. In this study, we explore the interaction mechanisms of hyaluronic acid (HA), a linear anionic polysaccharide composed of repeating disaccharide units of d-glucuronic acid and N-acetyl-d-glucosamine connected by alternating β-1,3 and β-1,4 glycosidic linkages, and its octanoylated derivates (OHA) with liposomes using extensive coarse-grained molecular dynamics simulations. The octyl moieties of OHA spontaneously inserted into the phospholipid bilayer of liposomes, leading to their effective coating onto the surface of liposome and enhancing their structural stability. Furthermore, encapsulating liposome with OHA neutralized their surface potential, interfering with the formation of a protein corona known to contribute to liposomal immune clearance. Importantly, the encapsulated OHA maintained its selectivity and therefore targeting ability for CD44, which is often overexpressed in tumor cells. These molecular-scale findings shed light on the interaction mechanisms between HA and liposomes and will be useful for the development of next-generation liposome-based drug delivery systems.

Synergistic Effects of Chemotherapy and Phototherapy on Ovarian Cancer Using Follicle-Stimulating Hormone Receptor-Mediated Liposomes Co-Loaded with SN38 and IR820.

We have developed an ovarian cancer-targeted drug delivery system based on a follicle-stimulating hormone receptor (FSHR) peptide. The lipophilic chemotherapeutic drug SN38 and the photosensitizer IR820 were loaded into the phospholipid bilayer of liposomes. The combination of chemotherapy and phototherapy has become a promising strategy to improve the therapeutic effect of chemotherapy drugs on solid tumors. IR820 can be used for photodynamic therapy (PDT), effectively converting near-infrared light (NIR) into heat and producing reactive oxygen species (ROS), causing damage to intracellular components and leading to cell death. In addition, PDT generates heat in near-infrared, thereby enhancing the sensitivity of tumors to chemotherapy drugs. FSH liposomes loaded with SN38 and IR820 (SN38/IR820-Lipo@FSH) were prepared using thin-film hydration-sonication. FSH peptide binding was analyzed using 1H NMR spectrum and Maldi-Tof. The average size and zeta potential of SN38/IR820-Lipo@FSH were 105.1 ± 1.15 nm (PDI: 0.204 ± 0.03) and -27.8 ± 0.42 mV, respectively. The encapsulation efficiency of SN38 and IR820 in SN38/IR820-Lipo@FSH liposomes were 90.2% and 91.5%, respectively, and their release was slow in vitro. FSH significantly increased the uptake of liposomes, inhibited cell proliferation, and induced apoptosis in A2780 cells. Moreover, SN38/IR820-Lipo@FSH exhibited better tumor-targeting ability and anti-ovarian cancer activity in vivo when compared with non-targeted SN38/IR820-Lipo. The combination of chemotherapy and photodynamic treatment based on an FSH peptide-targeted delivery system may be an effective approach to treating ovarian cancer.

Improved anti-breast cancer activity by doxorubicin-loaded super stealth liposomes.

PEGylation is currently used for the synthesis of stealth liposomes and to enhance the pharmacokinetic and biopharmaceutical properties of payloads. PEGylated dendron phospholipids can decrease the detachment of polyethylene glycol (PEG) from the liposomal surface owing to an increased hydrophobic anchoring effect on the phospholipid bilayer of liposomes and thus generating super stealth liposomes that are suitable for the systemic delivery of anticancer drugs. Herein, doxorubicin hydrochloride-loaded super stealth liposomes were studied for the treatment of breast cancer lung metastasis in an animal model. The results demonstrated that the super stealth liposomes had suitable physicochemical properties for in vivo administration and could significantly increase the efficacy of doxorubicin in breast cancer lung metastasis tumor-bearing mice compared to the free drug. The super stealth liposomes also increased doxorubicin accumulation inside the tumor tissue. The permanence of PEG on the surface of the super stealth liposomes favored the formation of a depot of therapeutic nanocarriers inside the tumor tissue by improving their permanence after stopping treatment. The doxorubicin-loaded super stealth liposomes increased the survival of the mouse tumor model. These promising results demonstrate that the doxorubicin-loaded super stealth liposomes could be an effective nanomedicine to treat metastatic breast cancer.

Tumor microcalcification-mediated relay drug delivery for photodynamic immunotherapy of breast cancer

Spatiotemporal targeting of tumor-associated macrophages (TAMs) and tumor cells is emerging as a promising strategy for tumor therapy. Tumor microcalcifications that specifically bind to bisphosphonates are potentially used to design efficient relay drug delivery nanosystems to achieve spatiotemporal drug modulation. Here, we developed manganese dioxide (MnO2)-embedded and LyP-1 peptide-labeled liposomal nanoparticles (NPs) for photodynamic immunotherapy of breast cancer; zoledronic acid (Zol) was encapsulated in the hydrophilic cavity of liposomes, and a hydrophobic photosensitizer (IR780) was embedded in the phospholipid bilayer of liposomes. These Lipo Zol/IR NPs generated O2 bubbles through MnO2 in response to H2O2 in the tumor microenvironment, leading to the degradation of the liposomal membrane, which triggered the release of Zol and provided O2 for photodynamic therapy. The released Zol attached to microcalcifications and was selectively phagocytosed by TAMs, leading to the induction of death or repolarization of TAMs from the immunosuppressive M2 phenotype to the immunostimulatory M1 phenotype. The remaining liposomal fragments embedded with IR780 then preferentially targeted tumor cells through LyP-1 peptide and produced abundant reactive oxygen species (ROS) under near infrared (NIR) laser irradiation, resulting in the death of tumor cells and mild immune activation. All in vitro and in vivo studies demonstrated the effective photodynamic and immunoregulatory performance of Lipo Zol/IR NPs. Statement of significanceSpatiotemporal targeting of tumor-associated macrophages (TAMs) and tumor cells remains a challenge in tumor photodynamic immunotherapy for promoting synergy and reducing side effects. Here, we developed tumor microcalcification-mediated relay drug delivery nanoliposomes for breast cancer therapy. H2O2 in the tumor microenvironment (TME) triggers the breakage of nanoliposomes, thereby causing the separation of zoledronic acid (Zol) and the photosensitizer IR780 and allowing them to perform their respective functions. Microcalcifications enable Zol to target TAMs, resulting in immunomodulation. LyP-1 guides IR780 to target tumor cells for PDT with adequate O2 supply. These nanoliposomes enable precise spatiotemporal targeting of different types of cells in the TME and promote the synergy between immunotherapy and PDT while ensuring the effectiveness of both methods.

Biomimetic Recognition-Based Bioorthogonal Host–Guest Pairs for Cell Targeting and Tissue Imaging in Living Animals

Biomimetic Recognition-Based Bioorthogonal Host–Guest Pairs for Cell Targeting and Tissue Imaging in Living Animals

Photoacoustic effect of azo derivatives modified by click reagents and parceled by liposomes

Photoacoustic (PA) imaging has been highlighted as one of the latest and the most promising biophotonic diagnostic modalities. As promising contrast agents, near-infrared (NIR) light-absorbing agents are highly in great demand. Here, the PA and photothermal (PT) effects of a series of NIR absorbing azo derivatives were characterized. Interestingly, compared with tetracyanoethylene (TCNE) and 7,7,8,8-tetracyanoquiodimethane (TCNQ), the click reagent 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquiodimethane (F4-TCNQ) caused the red shift to near infrared (NIR) region for the peaks of PA intensity of molecules. Moreover, symmetrical molecular structure of NIR dyes had better PA effect. The M2a (clicked by TCNQ) molecules were embedded into hydrophobic phospholipid bilayer of liposomes (M2a⊂L) and internalized into human breast cancer Michigan Cancer Foundation-7 (MCF-7) cell. The toxicity of the cell was low, because the cell viability reached amost 100%, which was evaluated through CCK-8 assays to determine the metabolic viability of MCF-7 cells, while the cell PA intensity was high (1.5 × 103). The systematical research of the NIR dyes not only provided a series promising NIR dyes for imaging and treatment, but also guided the design of contrast agents and PT agents which had high PA and PT effects.

The application of small organic π-conjugated discotic derivatives in photoacoustic imaging and photothermal conversion

Near-infrared absorbing dyes are catching people’s attention as they are committed to find materials with greater photoacoustic (PA) and photothermal (PT) effect. In this study, a new series of organic π-conjugated discotic derivatives synthesized via [2 + 2] click chemistry were introduced. The PA intensity and PT conversion effect of the derivatives were monitored. It was found that the π-conjugated discotic derivatives had a proper absorption peak and PA intensity by introducing the click regents. Furthermore, the PA intensity remained relatively high, while B12 molecules were embedded in hydrophobic phospholipid bilayer of liposomes (B12⊂L). The application in biological therapy for tumors become possible as the toxicity of B12⊂L was low. What’s more, when B12 molecules embedded in poly (N-isopropylacrylamide)-block-poly (2-nitrobenzyl methacrylate) (PNIPAM-b-PNBM) thermosensitive micelles were irradiated by laser, the molecules could take the place of direct temperature stimulus. This work affords us a way to solve the problem in which direct temperature stimulus is inapplicable.

Dorzolamide nanoliposome as a long action ophthalmic delivery system in open angle glaucoma and ocular hypertension patients

Importance: To reduce the frequency of dorzolamide eye drop administration and increasing the duration of action.Background: This study aims to compare the effect of dorzolamide loaded-nanoliposome with marketed dorzolamide HCl eye drop on intraocular pressure in primary open angle glaucoma and ocular hypertension patients.Design: A randomized study was conducted in a hospital.Participants: Twenty patients with primary open angle glaucoma or ocular hypertension (in both eyes) diagnosis were recruited as participants.Methods: Dorzolamide loaded-nanoliposome was prepared by thin layer hydration method and characterized. Intra ocular pressure were compared between the two groups who received marketed dorzolamide solution or dorzolamide-loaded nanoliposome.Main outcome measures: The main outcome measures include intraocular pressure initially (day 0) and on days 14 and 28 and adverse effect of dorzolamide-loaded nanoliposome eye drop.Results: Based on the results of repeated measure, intra ocular pressure was seen to decrease in both the groups. But these reductions in the intervention group (dorzolamide-loaded eye drop) were significantly higher than those in control group (p < 0.05).Conclusion: This study confirmed safety and long-lasting efficacy of dorzolamide loaded-nanoliposome eye drop. The highly enhanced permeation through the cornea can be attributed to similarity of phospholipid bilayer of liposomes to the biological membrane and their small particle size and positive zeta potential.

In vivo evaluation of electron mediators for the reduction of methemoglobin encapsulated in liposomes using electron energies produced by red blood cell glycolysis

Earlier studies have clarified that NADH and NADPH, re-energized repeatedly by red blood cell (RBC) glycolysis, can be used in extracellular chemical reactions, where electron energies are extracted by electron mediators, such as methylene blue (MB). The electron mediators, which are reduced by NAD(P)H, permeate both the membranes of RBC and phospholipid bilayer of liposomes encapsulating haemoglobin (Hb-vesicles, HbV) and reduce autoxidized ferric methemoglobin (metHb) in HbV to ferrous Hb. Moreover, in vitro screening study clarified some other potential electron mediators with comparable capacity to reduce metHb. Given this background, eight of these compounds: MB, 1,9-dimethyl MB, azure A, azure B (AB), azure, toluidine blue, brilliant cresyl blue and toluylene blue, were evaluated in both in vitro and in vivo studies in this work. Compared with MB as a reference, in vitro experiments demonstrated that most compounds caused effective metHb reduction of HbV in the presence of RBC. However, in vivo experiments of bolus injection of autoxidized HbV to rats (10 mL HbV/kg body weight) followed by injection of the dye (1.53 mL/kg body weight, 2.6 mM) led to some differences from in vitro results. Effective metHb reduction was found for the combination of AB. To evaluate AB effectiveness further, a haemorrhagic shock and resuscitation model was used, where the rats were resuscitated with HbV. When the level of metHb increased to 50%, a dye solution was injected. Again, AB caused sufficient reduction of metHb. Through these in vivo experiments, this study clarified that AB is a suitable electron mediator to prolong the functional lifetime of HbV.

An EPR spin probe study of liposomes from sunflower and soybean phospholipids

Comparative properties of lecithin-based liposomes prepared from the mixed phospholipids of sunflower seeds, soybean and egg yolk were investigated by electron paramagnetic resonance (EPR) spectroscopy. For these investigations, stable nitroxide radicals, 1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl 5,7-dimethyladamantane-1-carboxylate (DMAC-TEMPO), 5-doxylstearic acid (5-DSA) and 16-doxylstearic acid (16-DSA) were used as spin probes. Binding of the spin probes to the liposome membranes resulted in a substantial increase of the apparent rotational diffusion correlation times. The EPR spectra of the incorporated nitroxides underwent temperature-dependent changes. For every spin probe, values of apparent enthalpy and entropy of activation were calculated from the temperature dependence of rotational diffusion correlation times via Arrhenius equation. In case of DMAC-TEMPO, the data point to differences between the phospholipid bilayer of liposomes derived from sunflower and soy lecithin, and some similarity between the sunflower and egg yolk liposomes. Anisotropic hyperfine interaction constants of DMAC-TEMPO and 16-DSA included in the liposomes have been analyzed and attributed to different micropolarity of the surroundings of the spin probes. The kinetics of EPR signal decay of DMAC-TEMPO in the presence of 2,2′-azobis(2-amidinopropane) suggest the better stability of the sunflower liposomes to lipid peroxidation as compared to the liposomes prepared from soy lecithin.

Nano-confined squaraine dye assemblies: new photoacoustic and near-infrared fluorescence dual-modular imaging probes in vivo.

For the purpose of near-infrared (NIR) fluorescence and photoacoustic (PA) tomography dual-modular imaging, self-assembly of squaraine (SQ) dyes is constructed in the hydrophobic phospholipid bilayers of liposomes (SQ⊂L) with variable mixing ratios of SQ and phospholipids from 1:500 to 1:10 (w/w). When doping minimal amounts of SQ, molecularly dispersed SQ in bilayers shows remarkable fluorescence. Interesting, the PA signal is enhanced with increase of SQ in the nanoconfined bilayer region, which is attributed to the formation of SQ-based H-aggregates and enhanced thermal conversion efficiency (η). SQ⊂L shows satisfactory chemical and thermal stabilities and photobleaching resistance. SQ⊂L is well-distributed in the cytoplasm of MCF-7 cells and its fluorescence signal remains for 7 days without dramatic quenching owing to the good stability of SQ⊂L. Furthermore, SQ⊂L is subjected to in vivo NIR fluorescence imaging to evaluate the whole-body biodistribution in organ level. Particularly, PA imaging with deeper tissue penetration capability is utilized to investigate the heterogeneous distribution SQ⊂L inside solid tumor. The majority of SQ⊂L are enriched in the area where the blood vessels are generated, implying that the liposomal nanocarriers exhibit lower tumor tissue penetration capability after the vascular leakage. This result is validated by histological examination of tumor tissue in parallel.

A Liposomal Formulation Able to Incorporate a High Content of Paclitaxel and Exert Promising Anticancer Effect

A liposome formulation for paclitaxel was developed in this study. The liposomes, composed of naturally unsaturated and hydrogenated phosphatidylcholines, with significant phase transition temperature difference, were prepared and characterized. The liposomes exhibited a high content of paclitaxel, which was incorporated within the segregated microdomains coexisting on phospholipid bilayer of liposomes. As much as 15% paclitaxel to phospholipid molar ratio were attained without precipitates observed during preparation. In addition, the liposomes remained stable in liquid form at 4°C for at least 6 months. The special composition of liposomal membrane which could reduce paclitaxel aggregation could account for such a capacity and stability. The cytotoxicity of prepared paclitaxel liposomes on the colon cancer C-26 cell culture was comparable to Taxol. Acute toxicity test revealed that LD50 for intravenous bolus injection in mice exceeded by 40 mg/kg. In antitumor efficacy study, the prepared liposomal paclitaxel demonstrated the increase in the efficacy against human cancer in animal model. Taken together, the novel formulated liposomes can incorporate high content of paclitaxel, remaining stable for long-term storage. These animal data also demonstrate that the liposomal paclitaxel is promising for further clinical use.

Liposomes for targeting of antigens and drugs: Immunoadjuvant activity and liposome-mediated depletion of macrophages

Liposomes have proven their use as a tool in various immunological studies. In our own studies, both their application as antigen carriers and as drug carriers appeared to be useful. Immune responses were elicited against free soluble protein antigens and against the same antigens in a liposome-associated (particulate) form, in order to compare both types of response. Since we were especially interested in the role of splenic macrophages in both types of response, we developed a liposome-mediated macrophage suicide approach, based on the liposome-mediated internalization of the small hydrophilic molecule clodronate in macrophages. This molecule has a very short half life when released in the circulation, but does not easily cross phospholipid bilayers of liposomes or cell membranes. As a consequence, once ingested by a macrophage in a liposome-encapsulated form, it will be accumulated within the cell as soon as the liposomes are digested with the help of its lysosomal phospholipases. At a certain intracellular clodronate concentration, the macrophage is eliminated by apoptosis. Given the fact that neither the liposomal phospholipids chosen nor clodronate are toxic to other (non-phagocytic) cells, this method has proven its efficacy for depletion of macrophage subsets in various organs. In several cases, organ-specific depletion can be obtained by choosing the right administration route for the clodronate liposomes.

Magnetic resonance study of the transmembrane nitrite diffusion

Nitrite ( NO 2 - ) , being a product of metabolism of both nitric oxide (NO ) and nitrate ( NO 3 - ), can accumulate in tissues and regenerate NO by several mechanisms. The effect of NO 2 - on ischemia/reperfusion injury was also reported. Nevertheless, the mechanisms of intracellular NO 2 - accumulation are poorly understood. We suggested significant role of nitrite penetration through biological membranes in the form of undissociated nitrous acid (HNO 2). This hypothesis has been tested using large unilamellar phosphatidylcholine liposomes and several spectroscopic techniques. HNO 2 transport across the phospholipid bilayer of liposomes facilitates proton transfer resulting in intraliposomal acidification, which was measured using pH-sensitive probes. NO 2 - -mediated intraliposomal acidification was confirmed by EPR spectroscopy using membrane-impermeable pH-sensitive nitroxide, AMC (2,2,5,5-tetramethyl-1-yloxy-2,5-dihydro-1H-imidazol-3-ium-4-yl)-aminomethanesulfonic acid (p K 5.25), and by 31P NMR spectroscopy using inorganic phosphate (p K 6.9). Nitrite accumulates inside liposomes in concentration exceeding its concentration in the bulk solution, when initial transmembrane pH gradient (alkaline inside) is applied. Intraliposomal accumulation of NO 2 - was observed by direct measurement using chemiluminescence technique. Perfusion of isolated rat hearts with buffer containing 4 μM NO 2 - was performed. The nitrite concentrations in the effluent and in the tissue, measured after 1 min perfusion, were close, supporting fast penetration of the nitrite through the tissue. Measurements of the nitrite/nitrate showed that total concentration of NO x in myocardium increased from initial 7.8 to 24.7 μM after nitrite perfusion. Physiological significance of passive transmembrane transport of NO 2 - and its coupling with intraliposomal acidification are discussed.

Cell Activation of Human Macrophages by Lipoteichoic Acid Is Strongly Attenuated by Lipopolysaccharide-binding Protein

Cell Activation of Human Macrophages by Lipoteichoic Acid Is Strongly Attenuated by Lipopolysaccharide-binding Protein

“In Vivo” Depletion of Macrophages by Liposome-Mediated “Suicide”

Publisher Summary Macrophages are multifunctional cell and play a key role in natural and acquired host defense reactions, in homeostasis, and in the regulation of numerous biological processes. The main tools used are phagocytosis followed by intracellular digestion and production and release of soluble mediators, such as cytokines, chemokines, and nitric oxide (NO). Macrophages can be found as resident cells in all organs of the body, and they can be recruited to sites of inflammation. The depletion of macrophages followed by functional studies in such macrophage-depleted animals forms a generally accepted approach to establish their role in any particular biomedical phenomenon. The methods for depletion of macrophages are based on the liposome-mediated intracellular delivery of the bisphosphonate clodronate. Liposomes are used as a Trojan horse to get the small clodronate molecules into the macrophage. Once ingested by macrophages, the phospholipid bilayers of liposomes are disrupted under the influence of lysosomal phospholipases. The strongly hydrophilic clodronate molecules intracellularly released do not escape from the cell. As a result, the intracellular clodronate concentration increases as more liposomes are ingested and digested. At a certain clodronate concentration, irreversible damage causes the macrophage to be killed by apoptosis. Free clodronate molecules show an extremely short half-life in circulation and body fluids. They are removed by the renal system. Clodronate in its free form is used widely as a drug for the treatment of malignant hypercalcemia and painful bone metastasis caused by hormone-refractory prostate cancer, emphasizing its nontoxic nature.

Green tea polyphenols react with 1,1-diphenyl-2-picrylhydrazyl free radicals in the bilayer of liposomes: direct evidence from electron spin resonance studies.

Free radical scavenging reactions of green tea polyphenols (GTP) were investigated with electron spin resonance (ESR) spectroscopy in the phospholipid bilayer of liposomes, using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical as a model. The results showed that (1) GTP reacts with DPPH radicals in the bilayer of liposomes of both 1-hexadecanoyl-2-[(cis,cis,cis,cis,cis,cis)-4,7,10, 13,16,19-docosahexaenoyl]-sn-glycero-3-phosphocholine (DHAPC) and 1, 2-di[cis-9-hexadecenoyl]-sn-glycero-3-phosphocholine) (DPPC); and (2) GTP protects DHAPC liposomes effectively from the oxidation initiated by DPPH radicals. These results provide direct evidence that GTP reacts with free radicals in the model membrane and support the hypothesis that GTP protects unsaturated phospholipids from oxidation by reacting directly with the radicals.

Liposomes as drug delivery vehicles for boron agents.

The successful treatment of cancer by boron neutron capture therapy (BNCT) requires the selective concentration of boron-10 within malignant tumors. The potential of liposomes to deliver boron-rich compounds to tumors has been assessed by examination of the biodistribution of boron delivered by liposomes in tumor-bearing mice. Small unilamellar vesicles have been found to stably encapsulate high concentrations of water-soluble ionic boron compounds. Alternatively, lipophilic boron-containing species have been embedded within the phospholipid bilayer of liposomes, and both hydrophilic and lipophilic boron compounds have been incorporated within the same liposome formulation. The biodistribution of boron was determined at several time points over 48 hr after i.v. injection of liposomal suspensions in BALB/c mice bearing EMT6 tumors. The tumor-selective delivery of boron by the liposomes was demonstrated as tumor-boron concentrations increased for several hours post-injection. Even at the low injected doses employed (6-18 mg boron/kg body weight) therapeutic tumor boron concentrations were observed (> 30 micrograms boron/g tissue) and high tumor/blood ratios were achieved (> 5). The most favorable results were obtained with the polyhedral borane Na3[a2-B20H1-NH2CH2CH2NH2]. Liposomes encapsulating this species produced a tumor boron concentration of 45 micrograms/g tissue at 30 hr post-injection, at which time the tumor/blood boron ratio was 9.3.

The structure of colloidal formulations of amphotericin B

Fluorescence quenching techniques have been used to identify the location of amphotericin B in liposomes and emulsions. Amphotericin B efficiently quenched the fluorescence of probes located in either the phospholipid bilayer of liposomes or the lecithin emulsifier layer of emulsions, but were without significant effect on the fluorescence of probes in the aqueous surroundings of liposomes or emulsions, or probes in the internal aqueous spaces of liposomes. From these data, and a consideration of the solubility of amphotericin B in solvent systems, it is suggested that amphotericin B in liposomes is present largely in the phospholipid bilayer, and not in the aqueous space or surrounding medium. Additionally, amphotericin B in an emulsion formulation is located in the lecithin emulsifier monolayer and not in the bulk of the oil droplet. These findings are consistent with current views of the mode of action of such formulations.

Effect of Triton X-100 on the physical properties of liposomes

The interaction of the nonionic detergent Triton X-100 with phospholipid bilayers of liposomes made of egg yolk phosphatidylcholine was studied through the behavior of several physical properties. The dielectric permittivity spectra between 30 kHz and 13 MHz, the viscosity, the density, and the d.c. conductivity (1 kHz) of aqueous liposomes suspensions at various mole ratios were measured at 22°C. For detergent-to-phospholipid ratios lower than 3, a dielectric relaxation process of characteristic frequency of about 50 kHz was recorded. This process does not appear for the liposomes in water, and becomes smaller and smaller for detergent-to-phospholipid ratios higher than 3. The viscosity of these suspensions showed a biphasic behavior, being remarkably increased by the detergent for concentration ratios lower than 3. The measured d.c. conductivity of these samples showed no relation with this process, being slightly increased when the detergent content is increased. As a conclusion of these results a well defined concentration range appears where the phospholipid organization changes forming highly asymmetrical structures.