Targeted delivery of anti-fungal agents
The present application discloses a targeting composition that actively targets chitin-like substances, such as those found in fungi, protists, arthropods, Alzheimer's plaques, etc. Methods are disclosed for preparation of chitin-targeted drug delivery vehicles composed of the targeting composition and one or more bioactive compounds.
1. A chitin targeting agent comprising the following structure:
wherein R 4a , R 4b , and R 6a are independently selected from Cl, amino, or hydroxy, the last two of which are optionally substituted by alkyl, alkylamino, alkylhydroxy, alicyclic, heterocyclic, aryl, and alkyl- or arylsulfonic acid, where each of the optional substituents may further be optionally substituted by one or more groups selected from the group consisting of hydroxy and amino,
wherein R 6b is linked to phospholipid-PEG n , where the number of PEG units, n, is about 10-250, phospholipid, or dendrimer (G 3 -G 10 ),
wherein the linker is composed of PEG, alkyl, heteroalkyl, heterocyclic, or aryl, and pharmaceutically acceptable salts thereof.
2. A targeted drug delivery vehicle comprising the chitin targeting agent of claim 1 , and further comprising a block copolymer micelle and one or more antifungal drugs.
3. A targeted drug delivery vehicle comprising the chitin targeting agent of claim 1 , and further comprising a liposome and one or more antifungal drugs.
4. A targeted drug delivery vehicle comprising the chitin targeting agent of claim 1 , and further comprising a nanodisc and one or more antifungal drugs.
5. A targeted drug delivery vehicle comprising the chitin targeting agent of claim 1 , and further comprising a dendrimer and one or more antifungal drugs.
6. A targeted drug delivery vehicle comprising the chitin targeting agent as in one of claims 2 - 5 wherein the antifungal drug consists of Amphotericin B.
7. A targeted drug delivery vehicle comprising the chitin targeting agent as in one of claims 2 - 5 wherein the antifungal drug is selected from the group consisting of an echinocandin, azole, allosamidin, anidulafungin, bifonazole, butenafine, butoconazole, candicidin, caspofungin, cerulenin, chloroxine, ciclopirox, clioquinol, clotrimazole, econazole, fluconazole, flucytosine, griseofulvin, itraconazole, ketoconazole, micafungin, miconazole, naftifine, natamycin, nystatin, oxiconazole, posaconazole, sertaconazole, terbinafine, terconazole, tioconazole, and voriconazole.
8. A targeted drug delivery vehicle comprising the chitin targeting agent as in one of claims 2 - 5 and further comprising a block copolymer micelle and one or more antifungal drugs, and one or more phospholipids.
9. A targeted drug delivery vehicle comprising the chitin targeting agent as in one of claims 2 - 5 and further comprising a liposome and one or more antifungal drugs, and one or more phospholipids.
10. A targeted drug delivery vehicle comprising the chitin targeting agent as in one of claims 2 - 5 and further comprising a nanodisc and one or more antifungal drugs, and one or more phospholipids.
11. A method of preparing a targeted drug delivery vehicle, comprising assembling into a micelle, liposome or nanodisc a phospholipid, a targeting agent of claim 1 and an antifungal drug wherein the phospholipid comprises phosphatidylethanolamine.
12. A method of preparing a targeted drug delivery vehicle, comprising assembling into a micelle, liposome or nanodisc a phospholipid, a targeting agent of claim 1 and an antifungal drug wherein the phospholipid comprises phosphatidylserine, phosphatidylinositol, phosphatidylinositol phosphate, phosphatidylglycerol, or phosphatidylglycerol phosphate, optionally covalently linked to polyethylene glycol.