Encochleation methods, cochleates and methods of use
View Patent ↗Disclosed are novel methods for making cochleates and cochleate compositions that include introducing a cargo moiety to a liposome in the presence of a solvent. Also disclosed are cochleates and cochleate compositions that include an aggregation inhibitor, and optionally, a cargo moiety. Additionally, anhydrous cochleates that include a protonized cargo moiety, a divalent metal cation and a negatively charge lipid are disclosed. Methods of using the cochleate compositions of the invention, including methods of administration, are also disclosed.
1. A cochleate composition comprising:
Amphotericin B;
a plurality of cochleates comprising soy phosphatidyl serine; and
0.2%-0.4% (w/w) methylcellulose; and
wherein the weight ratio of soy phosphatidyl serine to Amphotericin B is about 5:1.
2. The composition of claim 1 , wherein the plurality of cochleates has a mean diameter of less than about 600 nm.
3. The composition of claim 1 , wherein the plurality of cochleates has a mean diameter of less than about 500 nm.
4. The composition of claim 1 , wherein the size distribution of the plurality of cochleates is less than about 700 nm.
5. The composition of claim 1 , wherein the size distribution of the plurality of cochleates is less than about 550 nm.
6. The composition of claim 1 , wherein the composition is in the form of a nasal spray.
7. A pharmaceutical composition comprising a therapeutically effective amount of the cochleate composition of claim 1 and a pharmaceutically acceptable carrier.
8. A method of treating a subject that can benefit from the administration of Amphotericin B, comprising the step of:
administering the pharmaceutical composition of claim 7 to said subject, such that the subject is benefited.
9. The method of treatment according to claim 8 , wherein the administration is by a mucosal or a systemic route.
10. The method of treatment according to claim 8 , wherein the administration is a mucosal route selected from the group consisting of oral, intranasal, intraocular, intrarectal, intravaginal, topical, buccal and intrapulmonary.
11. The method of treatment according to claim 8 , wherein the administration is intranasal.
12. The method of treatment according to claim 11 , wherein the pharmaceutical composition is delivered in a form selected from the group consisting of a spray, a nebulae, a mist, an atomized vapor, an irrigant, an aerosol, a wash, and an inhalant.
13. The method of claim 8 , wherein the pharmaceutical composition is used to treat rhinosinusitis.
14. The method of treatment according to claim 8 , wherein the administration is by a systemic route selected from the group consisting of intravenous, intramuscular, intrathecal, subcutaneous, transdermal and intradermal.
15. The method of claim 8 , Amphotericin B is administered to treat-parasitic disorders.
16. The method of claim 8 , wherein the pharmaceutical composition is administered to treat asthma.
17. The method of claim 8 , wherein the pharmaceutical composition is administered to treat at least one disorder selected from the group of consisting of asthma, chronic rhinosinusitis, allergic fungal sinusitis, sinus mycetoma, non-invasive fungus induced mucositis, and non-invasive fungus induced intestinal mucositis.