Liposomal formulations for oral immunotherapy: in-vitro stability in synthetic intestinal media and in-vivo efficacy in the mouse.

The aim of this work was to develop a liposomal formulation which could act as a carrier for allergens during oral desensitization therapy. A model protein, ovalbumin, was associated with negatively charged, multilamellar vesicles of various compositions and their stability in the presence of synthetic intestinal media (bile salt, pancreatic enzymes and their combination) was investigated. Liposomes containing soya phosphatidylcholine as the main lipid, regardless of their cholesterol content (20-40%), were unable to protect ovalbumin against the combined action of pancreatic enzymes and bile salt. In contrast, liposomes prepared from distearoylphosphatidylcholine and cholesterol (6:3.5 molar ratio) were more stable: about 50% of the lipid remained as liposomes after a 4-h incubation at 37 degrees C and intact ovalbumin could be demonstrated therein by immunoblotting. The immunomodulating properties of liposomes were tested by following changes in serum IgE levels (by passive cutaneous anaphylaxis) in Balb/C mice sensitized to ovalbumin, after feeding various preparations. In this model, free ovalbumin was able to provoke a premature fall in IgE levels, and liposomes, whatever their composition, contributed no further effect.

[The effect of omega-3 fatty acids on risk factors for cardiovascular diseases].

UNLABELLED: Cardiovascular disease (CVD) is associated with dyslipidemia and frequently with insulin resistance, both of which are in general no alleviated by antilipidemic drugs. Our objective was to examine whether a dietary supplement containing omega-3 fatty acids (n-3 FA) can reduce the levels of serum lipids, fasting insulin and glucose in documented CVD patients treated by statins or bezafibrates. In a double-blind placebo-controlled trial of parallel design, 52 patients, age 69.2 years +/- 3.6 treated by antilipidemic drugs, were randomly assigned to receive daily 7 gr of a dietary concentrated supplement containing 67% n-3 FA (185 mg EPA and 465 mg/g DHA) in a form of spread (Yamega Ltd, Israel) or olive oil spread (placebo) and recommended to reduce the consumption of omega-6 fatty acids for 12 weeks. The average values +/- SD before and after dietary supplementations were compared. RESULTS: 44 patients (23 in the n-3 FA group) completed the study. In the n-3FA group we observed a significant decrease (p < 0.05) of total cholesterol (12.2%). LDL-cholesterol (16.8%), triglycerides (36.1%), insulin in hyperinsulinemic subjects (> 20 microunits/ml) (34.9%), and no significant changes in HDL-cholesterol and glucose. No hyperglycemia was detected. In the olive oil group we observed a significant decrease (p < 0.05) in the LDL-cholesterol values of 15.5% and no significant changes in the other parameters. No side effects were reported during the study in any of the participants. Our findings demonstrate that the incorporation of the dietary supplement containing EPA and DHA omega-3 fatty acids reduces significantly the above risk factors for CVD.

[Analgesic therapy of cancer outpatients]. / Protivobolevaia terapiia u onkologicheskikh bol'nykh v ambulatornykh usloviiakh.

The results of treatment of 164 out-patients with far advanced malignancies for chronic pain syndrome are discussed. It was found that subarachnoid, peridural and sacral blocks with alcohol, phenol glycerine and carbolic acid can relieve pain for a long time, improve general condition and save narcotic analgetics. The most effective proved to be peridural block by phenolglycerine which induced analgesia in 67% of cases and maintained it for 45 days.

Optimization and characterization of freeze-dried multilamellar liposomes incorporating different standardized allergen extracts.

Desensitization therapy for type I allergy is now current practice. Liposomes have been proposed as a support for allergens to improve safety and effectiveness. The aim of this work was to optimize liposomal formulations of three different standardized allergen extracts and to test their allergenicity in vitro and in a preclinical trial. Allergen extracts (Dactylis glomerata, Dermatophagoides pteronyssinus, and cat hair and dander) were associated with multilamellar liposomes of varying compositions at different pH. Liposome-bound allergens were quantified by RAST inhibition after ultracentrifugation, and analyzed qualitatively by SDS-PAGE followed by immunoblotting. Their allergenicity was assessed by basophil degranulation in vitro, as compared with the allergenicity of an aqueous extract, and by skin tests in allergic subjects. The best association, about 50% of the added allergen, was obtained with negatively charged liposomes, when the pH of the allergen solution was adjusted so as to impart a net positive charge to the proteins. One-third of the liposome-associated allergens was located on the surface of the liposomes and was free to interact with antibody, as shown by RAST inhibition assays and the basophil degranulation test; the remaining two-thirds was encapsulated within the liposomes. All the major immunoreactive proteins in the extract were included. These liposomes could be readily freeze-dried and reconstituted without changing their properties. This study reveals the allergenic characteristics of liposomes and suggests their potential use in the treatment of allergic patients.