Cochleates made with soy phosphatidylserine
Unpurified or low pure soy phosphatidylserine is used to make cochleates. The cochleates contain about 40-74% soy phosphatidylserine, a multivalent cation and a biological active. A preferred cochleate contains the antifungal agent amphotericin B.
1. A method for preparing cochleates comprising:
(a) providing a suspension of liposomes in an aqueous medium, wherein the liposomes comprise (i) a lipid bilayer comprising soy phosphatidylserine in an amount of about 40%-55% by weight of the lipid bilayer, and (ii) a bioactive drug;
(b) contacting the suspension of liposomes of (a) with a multivalent cation,
thereby preparing cochleates.
2. The method of claim 1 wherein the lipid bilayer comprises about 45%-55% by weight soy phosphatidylserine.
3. The method of claim 1 wherein step (a), the aqueous medium containing the suspension of liposome is a buffered environment having a pH of 6.5-7.5, and the the bioactive drug is at pH 10 or higher prior to addition to the liposomes.
4. The method of claim 3 wherein the suspension of liposomes is buffered with phosphate.
5. The method of claim 1 wherein the bioactive drug is at least one member selected from the group consisting of a protein, a small peptide, a polynucleotide, an antiviral agent, an anesthetic, an antibiotic, an antifungal agent, an anticancer agent, an immunosuppressant, a steroidal anti-inflammatory agent, a non-steroidal anti-inflammatory agent, a tranquilizer, a nutritional supplement, an herbal product, a vitamin and a vasodilatory agent.
6. The method of claim 5 wherein the bioactive drug is at least one member selected from the group consisting of an aminoglycoside, amphotericin B, acyclovir, adriamycin, cabamazepine, curcumin, melphalan, nifedipine, indomethacin, naproxen, estrogens, testosterones, steroids, phenytoin, ergotamines, cannabinoids, rapamycin, propanidid, propofol, alphadione, echinomycine, miconazole nitrate, teniposide, a taxane, paclitaxel, and taxotere.
7. The method of claim 1 wherein the multivalent cation is Ca++, Zn++, Ba++, Mg++.
8. The method of claim 7 wherein the multivalent cation is Ca++.
9. The method of claim 1 , wherein the bioactive drug is amphotericin B.
10. The method claim 1 , wherein the bioactive drug is curcumin.
11. The method claim 1 , wherein the bioactive drug is amikacin.
12. The method claim 1 , wherein weight ratio of the lipid bilayer to the bioactive drug is between about 3:1 and about 20:1.
13. The method claim 1 wherein the method further comprises a step of adding bile salts to the suspension of liposomes of (a) before step (b) or adding bile salts to the cochleates after step (b), wherein the weight ratio of the lipid bilayer to the bile salts is between 20:1 and 0.5:1.