Large unilamellar vesicles (LUV) and method of preparing same

Drug – bio-affecting and body treating compositions – Solid synthetic organic polymer as designated organic active... – Polymer from ethylenic monomers only

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252316, 424 93, 424359, A61K 964

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active

040780520

ABSTRACT:
A process and resulting product for producing large unilamellar phosphatidylserine vesicles (LUV) in the diameter of about 2,000-12,000 A which may additionally encapsulate a drug. The large vesicles are prepared from an initial phosphatidylserine aqueous solution which is subjected to ultrasound or sonicated which produces small unilamellar vesicles (SUV) in the diameter range of 200-500 A. After the addition of calcium ion (Ca.sup.2+) in the molar concentration of about 1-10 mM (threshold 1-2 mM) and incubating for 30-60 minutes at room temperature above 10.degree. C and preferably 37.degree. C, intermediate cochleate lipid cylinders form. Finally, addition of a calcium chelating agent such as EDTA or EGTA to these cochleate cylinders produces by fusion the desired large closed spherical unilamellar vesicles (LUV). The intermediate cochleate form appears specific to the phospholipid serine utilized and to the calcium ion (Ca.sup.2+) incubating agent. Specific examples of drugs encapsulated in the phosphatidylserine LUV vesicles are Actinomycin D, cyclic 3'5'-adenosine monophosphate, Poly I Poly C, RNA, DNA, and arabinose cytocine and its phosphorylated analogs.

REFERENCES:
patent: 3069370 (1962-12-01), Jensen et al.
patent: 3607776 (1971-09-01), Santo et al.
patent: 3692899 (1972-09-01), Levy
Hackh's Chemical Dictionary, 4th Edition, 1969, pp. 230 & 231.
Papahadjopoulos et al.: Cochleate Lipid Cylinders: Formation by Fusion of Unilamellar Lipid Vesicles, Biochim. Biophys. Acta., 394: 483-491, (1975).
Papahadjopoulos et al.,: Cellular Uptake of Cyclic AMP Captured within Phospholipid Vesicles and Effect on Cell-Growth Behaviour, Biochim. Biophys. Acta., 363: 404-418, (1974).
The Condensed Chemical Dictionary, 8th Edition, Revised by Hawley, Van Nostrand Reinhold Co., (1971), pp. 16, 75, 330, 764.

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