PubMed Health⌕ Search

Biomedical subjects

Katarina Edwards

Publications and source records attributed to Katarina Edwards.

At least 19 recordsLinked to original sources
PubMed2007

Docosahexaenoic acid stabilizes soluble amyloid-beta protofibrils and sustains amyloid-beta-induced neurotoxicity in vitro.

Enrichment of diet and culture media with the polyunsaturated fatty acid docosahexaenoic acid has been found to reduce the amyloid burden in mice and lower amyloid-beta (Abeta) levels in both mice and cultured cells. However, the direct interaction of polyunsaturated fatty acids, such as docosahexaenoic acid, with Abeta, and their effect on Abeta aggregation has not been explored in detail. Therefore, we have investigated the effect of docosahexaenoic acid, arachidonic acid and the saturated fatty acid arachidic acid on monomer oligomerization into protofibrils and protofibril fibrillization into fibrils in vitro, using size exclusion chromatography. The polyunsaturated fatty acids docosahexaenoic acid and arachidonic acid at micellar concentrations stabilized soluble Abeta42 wild-type protofibrils, thereby hindering their conversion to insoluble fibrils. As a consequence, docosahexaenoic acid sustained amyloid-beta-induced toxicity in PC12 cells over time, whereas Abeta without docosahexaenoic acid stabilization resulted in reduced toxicity, as Abeta formed fibrils. Arachidic acid had no effect on Abeta aggregation, and neither of the fatty acids had any protofibril-stabilizing effect on Abeta42 harboring the Arctic mutation (AbetaE22G). Consequently, AbetaArctic-induced toxicity could not be sustained using docosahexaenoic acid. These results provide new insights into the toxicity of different Abeta aggregates and how endogenous lipids can affect Abeta aggregation.

Amyloid↗
PubMed2006

Transition metal-mediated liposomal encapsulation of irinotecan (CPT-11) stabilizes the drug in the therapeutically active lactone conformation.

PURPOSE: To determine whether entrapped transition metals could mediate the active encapsulation of the anticancer drug irinotecan into preformed liposomes. Further, to establish that metal complexation could stabilize liposomal irinotecan in the therapeutically active lactone conformation. MATERIALS AND METHODS: Irinotecan was added to preformed 1,2-distearoyl-sn-glycero-phosphocholine/cholesterol (DSPC/chol) liposomes prepared in CuSO4, ZnSO4, MnSO4, or CoSO4 solutions, and drug encapsulation was determined over time. The roles of the transmembrane pH gradient and internal pH were evaluated. TLC and HPLC were used to monitor drug stability and liposome morphology was assessed by cryo-TEM. RESULTS: Irinotecan was rapidly and efficiently loaded into preformed liposomes prepared in unbuffered (approximately pH 3.5) 300 mM CuSO4 or ZnSO4. For Cu-containing liposomes, results suggested that irinotecan loading occurred when the interior pH and the exterior pH were matched; however, addition of nigericin to collapse any residual transmembrane pH gradient inhibited irinotecan loading. Greater than 90% of the encapsulated drug was in its active lactone form and cryo-TEM analysis indicated dark intravesicular electron-dense spots. CONCLUSION: Irinotecan is stably entrapped in the active lactone conformation within preformed copper-containing liposomes as a result of metal-drug complexation.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Morphology of magnetically aligning DMPC/DHPC aggregates-perforated sheets, not disks.

The morphology of DMPC/DHPC mixtures at total lipid concentration cL = 5% (w/w) and DMPC/DHPC ratio q approximately 3, doped with small amounts of DMPG or CTAB, was investigated. 31P NMR was used to identify the magnetically aligning phase, and cryo-transmission electron microscopy (cryo-TEM) was employed for structural characterization. Magnetic alignment was found to occur between approximately 30 and approximately 45 degrees C, and cryo-TEM showed that the magnetically aligning phase consisted of extended sheets with a lacelike structure. The aggregates are best described as intermediates between two-dimensional networks of flattened, highly branched, cylindrical micelles and lamellar sheets perforated by large irregular holes. DHPC most likely covers the edges of the holes, while DMPC makes up the bilayer bulk of the aggregates. However, 20-43% of the DHPC takes part in the bilayer, corresponding to 6-12% of the bilayer being made up of DHPC. This fraction increases with increasing temperature. At temperatures above 45 degrees C, the aligning phase collapses.

Journal Article↗
PubMed2006

Effects of phospholipid hydrolysis on the aggregate structure in DPPC/DSPE-PEG2000 liposome preparations after gel to liquid crystalline phase transition.

Upon storage of phospholipid liposome samples, lysolipids, fatty acids, and glycerol-3-phosphatidylcholine are generated as a result of acid- or base-catalyzed hydrolysis. Accumulation of hydrolysis products in the liposome membrane can induce fusion, leakage, and structural transformations of the liposomes, which may be detrimental or beneficial to their performance depending on their applications as, e.g., drug delivery devices. We investigated in the present study the influence of phospholipid hydrolysis on the aggregate morphology of DPPC/DSPE-PEG2000 liposomes after transition of the phospholipid membrane from the gel phase to liquid crystalline phase using high performance liquid chromatography (HPLC) in combination with static light scattering, dynamic light scattering, and cryo-transmission electron microscopy (cryo-TEM). The rates of DPPC hydrolysis in DPPC/DSPE-PEG2000 liposomes were investigated at a pH of 2, 4, or 6.5 and temperatures of 22 degrees C or 4 degrees C. Results indicate that following phase transition, severe structural reorganizations occurred in liposome samples that were partially hydrolyzed in the gel phase. The most prominent effect was an increasing tendency of liposomes to disintegrate into membrane discs in accordance with an increasing degree of phospholipid hydrolysis. Complete disintegration occurred when DPPC concentrations had decreased by, in some cases, as little as 3.6%. After extensive phospholipid hydrolysis, liposomes and discs fused to form large bilayer sheets as well as other more complex bilayer structures apparently due to a decreased ratio of lysolipid to palmitic acid levels in the liposome membrane.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2006

Unilamellar vesicles obtained by simply mixing dioctadecyldimethylammonium chloride and bromide with water.

Optically clear dispersions of dioctadecyldimethylammonium bromide and chloride (DODAX, X = Br-, Cl-) in water can be obtained by simply mixing the amphiphiles at low concentrations (1 mM) and at a temperature safely above the gel to liquid crystalline phase transition temperature (Tm approximately 45-48 degrees C) of DODAX in water. Under these conditions, dynamic light scattering shows that, at room temperature, the dispersions contain two well-defined populations of large vesicles with average hydrodynamic radii (R(H)) of 80 and 337 nm for DODAB and of 69 and 247 nm for DODAC. Cryo-transmission electron microscopy (cryo-TEM) micrographs show that DODAX vesicles are unilamellar and polydisperse with apparent radius up to 800 nm. The vesicles are stable for at least 1 month according to the ageing time-dependence of the turbidity and molar absorption coefficient.

Absorption↗
PubMed2006

Therapeutically optimized rates of drug release can be achieved by varying the drug-to-lipid ratio in liposomal vincristine formulations.

The anti-tumor efficacy of liposomal formulations of cell cycle dependent anticancer drugs is critically dependent on the rates at which the drugs are released from the liposomes. Previous work on liposomal formulations of vincristine have shown increasing efficacy for formulations with progressively slower release rates. Recent work has also shown that liposomal formulations of vincristine with higher drug-to-lipid (D/L) ratios exhibit reduced release rates. In this work, the effects of very high D/L ratios on vincristine release rates are investigated, and the antitumor efficacy of these formulations characterized in human xenograft tumor models. It is shown that the half-times (T(1/2)) for vincristine release from egg sphingomyelin/cholesterol liposomes in vivo can be adjusted from T(1/2) = 6.1 h for a formulation with a D/L of 0.025 (wt/wt) to T(1/2) = 117 h (extrapolated) for a formulation with a D/L ratio of 0.6 (wt/wt). The increase in drug retention at the higher D/L ratios appears to be related to the presence of drug precipitates in the liposomes. Variations in the D/L ratio did not affect the circulation lifetimes of the liposomal vincristine formulations. The relationship between drug release rates and anti-tumor efficacy was evaluated using a MX-1 human mammary tumor model. It was found that the antitumor activity of the liposomal vincristine formulations increased as D/L ratio increased from 0.025 to 0.1 (wt/wt) (T(1/2) = 6.1-15.6 h respectively) but decreased at higher D/L ratios (D/L = 0.6, wt/wt) (T(1/2) = 117 h). Free vincristine exhibited the lowest activity of all formulations examined. These results demonstrate that varying the D/L ratio provides a powerful method for regulating drug release and allows the generation of liposomal formulations of vincristine with therapeutically optimized drug release rates.

Adenocarcinoma↗
PubMed2006

Cryo-TEM investigation of phase behaviour and aggregate structure in dilute dispersions of monoolein and oleic acid.

Cryo-transmission electron microscopy (cryo-TEM) was used to image the microstructure in dilute sonicated dispersions of monoolein and oleic acid. The aim of the study was to explore how different experimental parameters, such as sample composition, total lipid concentration, pH, and ageing affect the phase behaviour and aggregate structure. Our investigations show that a rich variety of lamellar and non-lamellar structures, including liposomes and particles of cubic and inverted hexagonal phase, may form depending on the experimental conditions. The results are analyzed and discussed in relation to existing phase diagrams and earlier investigations concerning phase- and structural behaviour in monoolein/oleic acid/water systems.

Colloids↗
PubMed2006

A novel 125I-labeled daunorubicin derivative for radionuclide-based cancer therapy.

INTRODUCTION: Auger electron emitters, such as (125)I, are getting increasingly wider recognition as alternatives to current anticancer treatments. The effectiveness of Auger electrons is strongly dependent on their proximity to DNA and is therefore considered as harmless outside the nucleus. METHODS: (125)I or (127)I was conjugated with Comp1, Comp2 or Comp3 - three derivatives of the chemotherapeutic drug daunorubicin. Their capacity factors, DNA-binding constants and exclusion parameters, and the degree of DNA fragmentation after incubating isolated DNA with our (127)I- or (125)I-conjugated daunorubicin derivatives were determined. Human breast adenocarcinoma (SK-BR-3) cells were incubated with the derivatives; fluorescent microscopy and autoradiography images were generated; and cell growth was monitored. RESULTS AND DISCUSSION: The capacity factor of (127)I-Comp1 was similar to those of daunorubicin and doxorubicin, whereas lower capacity factors of (127)I-Comp2 and (127)I-Comp3 suggested reduced interactions with lipid membranes. DNA exclusion parameters and binding constants of (127)I-Comp1 and (127)I-Comp2, but not of (127)I-Comp3, were similar to those of doxorubicin. Fluorescent microscopy and autoradiography images of SK-BR-3 cells revealed that (127)I-Comp1 and (125)I-Comp1 accumulated in tumor cell nuclei, whereas (127)I-Comp2 and (127)I-Comp3 were present predominantly in other cell compartments. The binding of (125)I-Comp1 to isolated chromosomal DNA led to major fragmentation. Incubation of SK-BR-3 cells with (125)I-Comp1 inhibited cell growth, whereas doxorubicin or (127)I-Comp1 administered at the same concentration had no effect on cell growth. Our results thus suggest that (125)I-Comp1 has the potential to become a new tool for anticancer therapy.

Cell Line, Tumor↗
PubMed2006

Physiochemical characterization of the Alzheimer's disease-related peptides A beta 1-42Arctic and A beta 1-42wt.

The amyloid beta peptide (A beta) is crucial for the pathogenesis of Alzheimer's disease. Aggregation of monomeric A beta into insoluble amyloid fibrils proceeds through several soluble A beta intermediates, including protofibrils, which are believed to be central in the disease process. The main reason for this is their implication in familial Alzheimer's disease with the Arctic amyloid precursor protein mutation (E693G). This mutation gives rise to early onset Alzheimer's disease, and synthetic A beta 1-40Arctic displays an enhanced rate of protofibril formation in vitro[Nilsberth C, Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K, Forsell C, Stenh C, Luthman J, Teplow DB, Younkin SG, Naslund J & Lannfelt L. (2001) Nat Neurosci4, 887-893]. To increase our understanding of the mechanisms involved in A beta aggregation, especially A beta monomer oligomerization into protofibrils and protofibril fibrillization into fibrils, the kinetics of A beta 1-42wt and A beta 1-42Arctic aggregation were examined under different physiochemical conditions, such as concentration, temperature, ionic strength and pH. We used size exclusion chromatography for this purpose, where monomers are separated from protofibrils, and fibrils are separated from protofibrils in a centrifugation step. The Arctic mutation significantly accelerated both A beta 1-42wt protofibril formation and protofibril fibrillization. In addition, we demonstrated that two distinct chemical processes - monomer oligomerization and protofibril fibrillization - were affected differently by changes in the micro-environment and that the Arctic mutation alters the peptide response to such changes.

Alzheimer Disease↗
PubMed2005

Formation of drug-arylsulfonate complexes inside liposomes: a novel approach to improve drug retention.

The development of procedures to enhance drug retention in liposomes is important in order to achieve therapeutically optimized rates of drug release from liposomal carriers. In this study, the ability of lipophilic weak base drugs to complex with arylsulfonates resulting in formation of intravesicular precipitates is investigated as a means to enhance drug retention. It is shown that the arylsulfonates benzenesulfonate and hydroxybenzenesulfonate (HBS) induce precipitation of ciprofloxacin and vinorelbine, two representative weak base drugs that are difficult to retain in liposomal systems. The most complete precipitation was observed at pH values corresponding to charge neutralization of the drug-arylsulfonate complex. HBS is shown to be a much more effective precipitating agent than benzenesulfonate. It is also shown that vinorelbine and ciprofloxacin can be loaded into large unilamellar vesicles (LUV) containing the calcium salt of HBS using an ionophore-based loading method. Following drug loading, the formation of intravesicular drug-arylsulfonate precipitates of vinorelbine and ciprofloxacin was observed by cryo-electron microscopy. In vitro release experiments showed substantial improvements in drug retention for both vinorelbine and ciprofloxacin when HBS was present as compared to standard loading procedures employing MgSO4 as the entrapped solute. In vivo release experiments for vinorelbine in NuNu mice indicated a half-time for release for HBS-containing LUV of approximately 30 h, compared to 6.4 h for LUV loaded employing MgSO4. It is suggested that encapsulation procedures employing HBS in the internal medium can improve the retention of drugs that are difficult to retain in liposomes, possibly leading to enhanced therapeutic properties.

Animals↗
PubMed2005

Effects of lipid segregation and lysolipid dissociation on drug release from thermosensitive liposomes.

Lysolipid-containing thermosensitive liposomes (LTSL) release their contents instantly when heated to temperatures close to their gel to liquid-crystalline phase transition temperature (TC). We have recently shown that during the melting transition these liposomes undergo major morphology changes, including the formation of open liposomes, bilayer discs, and pore-like defects. The hyperthermia-induced release of liposomal contents appears to depend on the presence and accumulation of membrane additives in grain boundaries, which enhance packing defects and, in the case of micelle-forming membrane additives, stabilize the bilayer rim of open liposome structures and transient membrane pores. In the present study, we used the fluorescent label 1-pyrenehexadecanoicacid (PHDA) and a radiolabelled lysolipid as markers for lysolipid membrane distribution and retention, respectively. PHDA dimer formation indicated local PHDA accumulation in cholesterol-free liposomes but not in cholesterol-containing liposomes. When LTSL were incubated at a temperature of 37 degrees C together with egg-phosphatidylcholine (EPC) multilamellar vesicles (MLVs) approximately 50% of the lysolipids transferred rapidly from LTSL to EPC MLVs. This transfer led to a significant reduction in the amount of carboxyfluorescein released from LTSL upon heating. Our results imply that poor retention of lysolipids in the LTSL membrane could also affect drug release characteristics of LTSL in vivo.

Biomarkers↗
PubMed2005

Substantial increases in idarubicin plasma concentration by liposome encapsulation mediates improved antitumor activity.

Idarubicin has been successfully encapsulated in cholesterol-free liposomes, however, little is known about how the rate of drug release from circulating liposomes influences therapeutic activity. The studies described herein assess the attributes of a liposome formulation required to significantly increase the plasma levels of idarubicin and further establish whether increases in the circulation longevity of the drug mediate improved antitumor activity. Pharmacokinetic assessments of 6 different 3[H]-labelled liposome formulations were compared to free idarubicin. The highest idarubicin plasma concentrations were observed with DSPC/DSPE-PEG2000 liposomes formulated with 2 mol% DSPE-PEG2000 and 150 mM (iso-osmotic) internal citrate concentration. It was shown that increased levels of PEG-lipid incorporation augmented IDA release and the optimal liposomal formulation needed to be prepared under iso-osmotic conditions. For efficacy studies in a murine leukemia model, groups of 12-14 mice were treated i.v. with saline or equivalent doses (1, 2, 3 mg/kg) of free or liposomal IDA. Liposomal treatment groups exhibited a higher % increase in life span (ILS) as compared to equivalent doses of free drug. Efficacy studies completed in two drug resistant models, P388/ADR and MDA435LCC6/MDR1, demonstrated that neither the free nor liposomal formulation of idarubicin was therapeutically active. Encapsulation of IDA in liposomes increased antitumor activity in an IDA sensitive model, however, the significant increase in plasma drug levels was not sufficient to overcome multidrug resistance.

Animals↗
PubMed2005

Encapsulation of doxorubicin into thermosensitive liposomes via complexation with the transition metal manganese.

In the present study, doxorubicin was encapsulated into two thermosensitive liposome formulations which were composed of DPPC/MSPC/DSPE-PEG(2000) (90/10/4 mole ratio) or DPPC/DSPE-PEG(2000) (95/5 mole ratio). Doxorubicin loading was achieved through the use of a pH gradient or a novel procedure that involved doxorubicin complexation with manganese. Regardless of the initial drug-to-lipid ratios (D:L), the final D:L reached a maximum of 0.05 (w/w) when doxorubicin was encapsulated via a pH gradient for both thermosensitive liposome formulations. In contrast, the final maximum D:L achieved through manganese complexation was 0.2 (w/w), and this loading method did not affect temperature-induced drug release, with 85% of drug released from MSPC-containing liposomes within 10 min at 42 degrees C but <5% released over 60 min at 37 degrees C. When the thermosensitive liposomes prepared via the two different loading methods were injected into mice, similar plasma elimination profiles were observed. Cryo-transmission electron microscopy analysis indicated the presence of doxorubicin fiber bundles in liposomes loaded via pH gradient, compared to a stippled and diffuse morphology in those loaded via manganese complexation. To investigate the effect of intraliposomal pH on drug precipitate morphology, the A23187 ionophore (mediates Mn(2+)/H(+) exchange) was added to liposomes loaded with doxorubicin-manganese complex, and the stippled and diffuse appearance could be converted to one exhibiting fiber bundles after acidification of the liposome core. This suggests that the formation of doxorubicin-manganese complex is favored when the intraliposomal pH is >6.5. During the conversion to the fiber bundle morphology, no doxorubicin release was observed when A23187 was added to liposomes exhibiting a 0.05 (w/w), whereas a significant release was noted when the initial D:L was 0.2 (w/w). Following acidification of the liposomal interior and establishment of an apparent new D:L equilibrium, the measured D:L ratio was 0.05 (w/w). In conclusion, the manganese complexation loading method increased the encapsulation efficiency of doxorubicin in thermosensitive liposomes with no major impact on temperature-triggered drug release or pharmacokinetics.

Calcimycin↗
PubMed2005

Development and initial evaluation of PEG-stabilized bilayer disks as novel model membranes.

We show in this study that stable dispersions dominated by flat bilayer disks may be prepared from a carefully optimized mixture of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-5000] [PEG-DSPE(5000)]. By varying the content of the latter component, the average diameter of the disks can be changed in the interval from about 15 to 60 nm. The disks show excellent long-term stability, and their size and structure remain unaltered in the temperature range between 25 and 37 degrees C. The utility of the disks as artificial model membranes was confirmed and compared to uni- and multilamellar liposomes in a series of drug partition studies. Data obtained by isothermal titration calorimetry and drug partition chromatography (also referred to as immobilized liposome chromatography) indicate that the bilayer disks may serve as an attractive and sometimes superior alternative to liposomes in studies aiming at the investigation of drug-membrane interactions. The disks may, in addition, hold great potential for structure/function studies of membrane-bound proteins. Furthermore, we suggest that the sterically stabilized bilayer disks may prove interesting as carriers for in vivo delivery of protein/peptide, as well as conventional amphiphilic and/or hydrophobic, drugs.

Cholesterol↗
PubMed2005

Optimization and characterization of a sphingomyelin/cholesterol liposome formulation of vinorelbine with promising antitumor activity.

Vinorelbine (VRL) is a particularly lipophilic member of the vinca alkaloids which, as a class of drugs, exhibit improved cytotoxicity and therapeutic activity through increased duration of exposure. Here, we describe and optimize a sphingomyelin/cholesterol (SM/Chol) liposome formulation of VRL to maximize in vivo drug retention, plasma circulation time, and therapeutic activity. VRL was efficiently encapsulated (>90%) into 100 nm liposomes using an ionophore-mediated loading method. VRL retention in SM/Chol liposomes after intravenous injection in mice was dependent on drug-to-lipid ratio (D/L), with higher D/L ratios exhibiting increased drug retention (0.3 > 0.2 > 0.1, wt/wt) and improved pharmacokinetics. Cryo-electron microscopic examination of a high D/L ratio formulation indicated that the intravesicular regions of these liposomes were electron dense compared with empty liposomes. The optimized, high D/L ratio SM/Chol VRL formulation showed promising activity against subcutaneous B16 melanoma tumors compared with VRL or SM/Chol formulations of vincristine or vinblastine. Finally, the stability of the formulation was excellent (<5% drug leakage, >99% intact VRL, no changes in liposome size after 1 year at 2-8 degrees C). The optimized drug retention properties of the SM/Chol formulation of VRL, combined with its promising antitumor activity and pharmaceutical stability, make this formulation an excellent candidate for future clinical development.

Animals↗
PubMed2004

Direct observation and characterization of DMPC/DHPC aggregates under conditions relevant for biological solution NMR.

We have used cryo-transmission electron microscopy (cryo-TEM) for inspection of aggregates formed by dimyristoylphosphatidylcholine (DMPC) and dihexanoylphosphatidylcholine (DHPC) in aqueous solution at total phospholipid concentrations cL < or = 5% and DMPC/DHPC ratios q < or = 4.0. In combination with ocular inspections, we are able to sketch out this part of phase-diagram at T = 14-80 degrees C. The temperature and the ratio q are the dominating variables for changing sample morphology, while cL to a lesser extent affects the aggregate structure. At q = 0.5, small, possibly disc-shaped, aggregates with a diameter of approximately 6 nm are formed. At higher q-values, distorted discoidal micelles that tend to short cylindrical micelles are observed. The more well-shaped discs have a diameter of around 20 nm. Upon increasing q or the temperature, long slightly flattened cylindrical micelles that eventually branch are formed. A holey lamellar phase finally appears upon further elevation of q or temperature. The implications for biological NMR work are two. First, discs prepared as membrane mimics are frequently much smaller than predicted by current "ideal bicelle" models. Second, the q approximately 3 preparations used for aligning water-soluble biomolecules in magnetic fields consist of perforated lamellar sheets. Furthermore, the discovered sequence of morphological transitions may have important implications for the development of bicelle-based membrane protein crystallization methods.

Dimyristoylphosphatidylcholine↗
PubMed2004

Effects of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers on structure and stability of liposomal dioleoylphosphatidylethanolamine.

The effects caused by poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO; Pluronic) copolymers on the structure and stability of dioleoylphosphatidylethanolamine (DOPE) liposomes were studied by means of turbidity, leakage, and cryo-transmission electron microscopy investigations. The results show that by inclusion of Pluronics in the DOPE dispersion it is possible to stabilize the lamellar Lalpha phase and to produce liposomes that are stable and nonleaky at low pH (pH 5). The stabilizing capacity was observed to depend critically on the molecular composition of the Pluronics. Block copolymers with comparably long PPO and PEO segment lengths, such as F127 and F108, most effectively protected DOPE liposomes prepared at high pH from aggregation and subsequent structural rearrangements induced by acidification. A sufficiently long PPO block was found to be the most decisive parameter in order to obtain adequate coverage of the liposome surface at low Pluronic concentrations. Upon increasing the copolymer concentration, however, Pluronics with comparably short PPO and PEO segment lengths, such as F87 and P85, could also be used to stabilize the DOPE liposomes. Essentially the same trends were observed when the Pluronics were added to preformed DOPE liposomes instead of being included in the preparation mixture. In this case the least effective copolymers failed, however, to completely prevent the DOPE liposomes from releasing encapsulated hydrophilic markers.

Cryoelectron Microscopy↗