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Biomedical subjects

J Estelrich

Publications and source records attributed to J Estelrich.

26 records · Page 2Linked to original sources

Preparations of synthetic phospholipids promote procoagulant activity on damaged vessels: studies under flow conditions.

BACKGROUND: The possibility of developing synthetic platelet substitutes that could promote hemostasis with prolonged shelf-life and increased safety is an appealing one. STUDY DESIGN AND METHODS: Preparations containing synthetic phospholipids were incorporated into blood samples (1.15 mg/mL) in which platelets and white cell counts had been experimentally reduced by a filtration procedure. Vesicles containing phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), or combinations of PC and PE and of PC and PS were tested in this system. Blood was recirculated (10 min; shear rate, 250/sec) through a perfusion chamber containing vascular segments. The ability of the various phospholipid preparations to promote fibrin formation on the damaged subendothelium was evaluated morphometrically and expressed as the percentage of fibrin coverage. Generation of thrombin in the system was monitored through the measurement of prothrombin fragments 1 and 2. RESULTS: Vesicles containing PC, PI, PE:PC (1:1), or PS:PC (1:3) increased fibrin deposition on the subendothelium (64.5 +/- 9.8%, 32.7 +/- 6.3%, 58.3 +/- 6.5%, and 46.6 +/- 15.2%, respectively; p < 0.01 vs. 11.5 +/- 1.2% in thrombocytopenic blood). Vesicles containing PE, PS, or PS:PC (3:1) did not show procoagulant effect. CONCLUSION: Synthetic phospholipid preparations promote a local procoagulant activity at sites of vascular damage when they are incorporated into thrombocytopenic blood maintained under flow conditions.

Animals↗

Influence of the fluidity of liposome compositions on percutaneous absorption.

The penetration into the stratum corneum of fluorescein, as the acid form or as a sodium salt, encapsulated in liposomes formed by liquid- or gel-state phospholipids, with or without cholesterol, was investigated in humans by the stripping method. Liposomes prepared by extrusion were applied to the forearms of healthy human volunteers and 30 min later, strippings were performed. Fluorescein was extracted and determined by spectrofluorimetry. The skin penetration of sodium fluorescein was higher from fluid liposomes (phosphatidylcholine) than from rigid liposomes (hydrogenated phosphatidylcholine), but it was independent of the content of cholesterol. It seems that the liquid-crystalline state of the lipids is the main aspect involved in the fluidity of the liposome bilayer itself as well as in the interaction with the lipids of the stratum corneum. The similar enhanced penetration behavior obtained for unsaturated liposomes containing sodium or acid fluorescein seems to support the hypothesis of a previous destruction of the vesicles during its passage through the lipid intercellular pathway in the stratum corneum.

Adult↗

The effect of liposomes on skin barrier structure.

The present work deals with the 'in vivo' stripping technique to evaluate the percutaneous absorption of sodium fluorescein (NaFl) vehiculized in two different liposome preparations formed by phosphatidylcholine (PC) and lipids mimicking the stratum corneum (SC; ceramides, cholesterol, palmitic acid and cholesteryl sulphate), respectively. Furthermore, the possible effect of these vesicles on the SC lipid alkyl chain conformational order were evaluated at different depths of SC by non-invasive biophysical techniques: Corneometer, Tewameter and especially ATR-FTIR. The results of NaFl percutaneous absorption indicate the highest penetration in the case of incorporation in PC liposomes, which could be related to the increase in SC lipid disorder detected by ATR-FTIR, i.e. a decrease in skin barrier function. On the other hand, SC lipid liposomes have been shown to have a higher affinity for SC owing to the high amount of NaFl found in this layer, suggesting a greater reservoir capacity of SC when similar lipid composition formulation is applied. A lipid order increase is observed by infrared spectroscopy, when these types of liposomes are topically applied, resulting in a strong barrier effect. These results could be useful in designing specific liposomal topical applications.

Adult↗

The action of Triton X-100 and sodium dodecyl sulphate on lipid layers. Effect on monolayers and liposomes.

The action of two detergents, Triton X-100 and sodium dodecyl sulphate (SDS), on large, unilamellar liposomes was determined as liposome size variation, polydispersity and ability to release a soluble marker from liposomes. Triton X-100 produced stronger effects than SDS. Nevertheless, these differences in behaviour of such detergents could not be deduced from the interaction of the detergents with monolayers of the same composition as liposomes.

1,2-Dipalmitoylphosphatidylcholine↗

Encapsulation of doxorubicin in neutral liposomes by passive methods: evidence of drug-lipid interaction at neutral pH.

Doxorubicin, an antineoplastic agent, was encapsulated in liposomes of dipalmitoylphosphatidylcholine with or without cholesterol, by the extrusion procedure. Doxorubicin was added to the lipid before drying, or was present in the rehydration buffer, and the influence of the method of encapsulation on size and polydispersity was determined by photon correlation spectroscopy. Results showed an important interaction between doxorubicin and liposomes, although cholesterol-containing vesicles were those that underwent the strongest insertion of the drug. One important parameter, which determined the extension of such interaction, was the curvature of the vesicle bilayer. So, liposomes extruded through a 50 nm membrane filter suffered the highest relative size variation in comparison with empty liposomes. Doxorubicin also produced an increase in polydispersity of vesicle population; therefore its presence resulted in some fusion and/or aggregation processes. The stability of liposomes was dependent on lipid content, on the method of drug trapping and on the presence or absence of such drug. Encapsulation efficiency seemed to be inversely related to liposome stability. Maximal values, which never exceed 0.015 +/- 0.005 mumol of drug per mumol of lipid, were obtained when the drug was dried together with the lipids.

1,2-Dipalmitoylphosphatidylcholine↗

Physical stability of different liposome compositions obtained by extrusion method.

Six different liposome compositions were evaluated according their physical stability. The compositions used were (in mole ratio): dipalmitoylphosphatidylcholine (DPPC): DPPC:cholesterol (CHOL) (1:1), DPPC:CHOL (1:6:1), DPPC:CHOL:sphingomyelin (SFM) (7:2:1), DPPC:CHOL:stearylamine (STE) (8:5:1) and DPPC:CHOL:dicetyl phosphate (DCP) (8:5:1). The liposomes were obtained by the extrusion method, through polycarbonate membranes of 0.1 micron pore size. The captured volume, number of lamellae, size and polydispersity of the vesicle populations were determined for all compositions. The physical stability was checked at -20 degrees C, room temperature, 4 degrees C and 50 degrees C by determining the changes in vesicle size over a maximum of 40 days. The process of aggregation and/or fusion was observed by photon correlation spectroscopy. From the results, we can establish that the above compositions are metastable at a temperature of 50 degrees C. On the other hand, values of captured volume were smaller than predicted by theory. This fact can be explained by the non-sphericity of extruded vesicles. In relation to the stability, the introduction of CHOL in the formulation allows keeping the vesicles at 4 degrees C. In contrast, liposomes containing only DPPC are very stable at room temperature. Compositions with a high stability are those that have present SFM or STE. The latter keeps the structural bilayer at temperatures < 0 degrees C without cryoprotectors. Both the lipids, STE and DCP, form vesicles with a higher number of lamellae.

Absorptiometry, Photon↗

[Relation between the viscosity of enteral diets and mechanical complications in their administration according to the nasogastric catheters].

OBJECTIVE: The use of enteral nutrition has increased enormously over the last few years and at the same time the standard indications for parenteral nutrition, whether in hospitals or at home, have gradually been defined. The most common way to administer enteral nutrition is intermittently and using gravity, through a nasogastric catheter or through gastrostomy. In our daily practice it has been observed that there was at times a considerable delay in the administration of the diet by means of a nasogastric catheter and the tube was sometimes blocked due to its small calibre and/or the excessive viscosity of the formula. It was therefore proposed to study the viscosities of polymeric enteral diets with and without fibre at this hospital to identify the relationship with the time taken for their intermittent, gravity-driven administration through different calibres of nasogastric catheter at the maximum flow rate. RESULTS: Some of the enteral diets under study exceeded the recommended time for intermittent administration by gravity (20-40 minutes). CONCLUSIONS: We feel it is essential for the product label to provide information on the optimal calibre of the nasogastric catheter required for administration of the product.

Drug Labeling↗