polidocanol and Hemolysis

To investigate the lytic effects of sodium tetradecyl sulphate (STS) and polidocanol (POL) on erythrocytes, platelets, endothelial cells and platelet-derived microparticle (PDMP) formation in vitro and the potential protective effects of serum albumin and agents such as procaine.. The effects of sclerosants were studied in blood samples obtained from normal individuals. Absorbance densitometry was used to assess the lytic effects of sclerosants on blood cells and cultured human microvascular endothelial cells (HMEC) in plasma and in saline. PDMP were quantified by flow cytometry.. Haemolysis occurred in whole blood at sclerosant concentrations greater than 0.25% for STS and above 0.45% for POL. Similar concentrations of both agents caused platelet and endothelial cell lysis. Both sclerosants released PDMP at low concentrations but destroyed PDMP at higher concentrations. Albumin significantly reduced the lytic effect of both sclerosants on all cells but had a greater inhibitory effect on POL. Protamine at 0.01% had a neutralising effect on STS, whereas procaine and lignocaine showed no such activity.. Sclerosants at therapeutic concentrations lyse blood cells and endothelial cells in vitro. This effect is strongly reduced by serum albumin possibly contributing towards the low incidence of thromboembolic complications of sclerotherapy.

Topics: Blood Platelets; Cell Line; Cytoprotection; Densitometry; Dose-Response Relationship, Drug; Endothelial Cells; Erythrocytes; Flow Cytometry; Hemolysis; Humans; Lidocaine; Polidocanol; Polyethylene Glycols; Procaine; Protamines; Sclerosing Solutions; Serum Albumin, Bovine; Sodium Tetradecyl Sulfate; Transport Vesicles

For improving the nasal absorption of poorly absorbable hydrophilic compounds, the suitability of a combination of a mucolytic agent, N-acetyl-L-cysteine (NAC), and a nonionic surfactant, polyoxyethylene (C25) lauryl ether (laureth-25), was examined. Rat studies with fluorescent isothiocyanate-labeled dextran (molecular weight ca. 4.4 kDa, FD-4) as a model hydrophilic compound revealed dramatic enhancement of nasal absorption when NAC and laureth-25 were simultaneously applied. The nasal bioavailability of FD-4 in saline solution was 8.2+/-0.6% but increased to 40.0+/-5.5% when 5% NAC and 5% laureth-25 were added. This synergistic enhancement could result from the mucolytic activity of NAC in reducing mucous viscosity by which the accessibilities of FD-4 and laureth-25 to the epithelial membrane were increased. Further rat studies proved that this formulation increased nasal absorption of salmon calcitonin. Absolute bioavailability from saline solution containing 5% NAC and 1% laureth-25 was 26.8+/-2.2%, 3.5 times that of the commercial calcitonin nasal spray Miacalcin (7.7+/-2.1%). The potential of the new formulation to cause tissue damage in terms of hemolytic activity and liberation of phospholipid from the nasal membranes was nil or slight. The combination of NAC and laureth-25 appears suitable for use in development of nasal products for poorly absorbable drugs, especially peptide and protein drugs.

Topics: Acetylcysteine; Animals; Area Under Curve; Biological Availability; Calcitonin; Chemistry, Pharmaceutical; Dextrans; Expectorants; Fluorescein-5-isothiocyanate; Fluorescent Dyes; Free Radical Scavengers; Hemolysis; Male; Molecular Weight; Nasal Mucosa; Pharmaceutical Preparations; Phospholipids; Polidocanol; Polyethylene Glycols; Rats; Rats, Wistar; Surface-Active Agents

Xiao zhi ling (XZL), which consists of Chinese nutgalls and aluminium potassium sulphate, is used as a local injection for the treatment of internal haemorrhoids in China. It is also used for endoscopic sclerotherapy of oesophageal varices. To date, however, it has not been compared with other sclerosants with regard to its safety and efficacy.. In the present study, the effect on the endothelium and the haemolytic and thrombosing effects of XZL were compared with those of 5% ethanolamine oleate and 1% polidocanol, using an endothelial cell line and red blood cells taken from rats and the dorsal marginal ear vein of rabbits. In addition, XZL was injected into the area surrounding varices in rats and its efficacy was studied endoscopically and histologically.. Xiao zhi ling reduced the size of varices in rats after causing severe damage in the injected region. Compared with the other two sclerosants, however, XZL had little effect on the endothelium and was the least haemolytic compound. Furthermore, XZL did not cause thrombosis in the injected vein of a rabbit.. These results suggest that XZL is another type of sclerosant with astringent rather than detergent properties. This compound should be used to treat oesophageal varices by paravariceal injection in smaller doses than 5% ethanolamine oleate and 1% polidocanol.

Topics: Alum Compounds; Animals; Astringents; Cattle; Cell Line; China; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Endothelium, Vascular; Erythrocytes; Esophageal and Gastric Varices; Hemolysis; Male; Oleic Acids; Polidocanol; Polyethylene Glycols; Rabbits; Rats; Rats, Wistar; Sclerosing Solutions; Sclerotherapy; Thrombosis

Stimulated by a patient with dyspnea, thrombocytopenia, and leukopenia after sodium morrhuate sclerotherapy, we studied the effect of this agent on the plasma coagulation and complement systems, the formed elements of the blood, and cultured human endothelial cells. The addition of sodium morrhuate to citrated plasma did not cause clotting or shorten the prothrombin time or partial thromboplastin time. Incubation of a 1:100 dilution of the clinical sodium morrhuate preparation in heparinized plasma led to a modest rise in [C3a]. The addition of the drug (dilutions 1:50 to 1:300) to granulocytes caused prompt aggregation (and, at the higher concentrations, granulocyte cytotoxicity [trypan blue exclusion; lactate dehydrogenase release]), but the same dilutions failed to aggregate platelets. However, 0.05% morrhuate added to washed red blood cells caused a prompt 84.0% (+/- 0.8% SEM) hemolysis, rendering the supernatant buffer a potent platelet aggregant. Not only was this sclerosing agent toxic to granulocytes and red cells, but a 1:1000 dilution of the drug also caused the destruction of 35.5% (+/- 6.6%) of cultured endothelial cells as measured by chromium 51 release. Three other agents in current use (ethanolamine oleate, sodium tetradecyl sulfate, and polidocanol) were studied and found to cause effects qualitatively similar to those of sodium morrhuate. We conclude that these drugs cause phlebosclerosis not primarily through induction of plasma coagulation, but by directly damaging endothelium and red cells, triggering platelets, and aggregating granulocytes at the venous wall endothelium. These effects likely derive from the surfactant properties of sodium morrhuate as well as its high arachidonate content.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Coagulation; Cell Aggregation; Cell Survival; Cells, Cultured; Complement Activation; Endothelium; Erythrocytes; Fatty Acids; Granulocytes; Hemolysis; Humans; Lymphocyte Activation; Neutrophils; Oleic Acids; Platelet Aggregation; Polidocanol; Polyethylene Glycols; Sodium Morrhuate; Sodium Tetradecyl Sulfate