Nanostructures for drug delivery
The present invention provides compositions, preparations, formulations, kits, and methods useful for treating subjects having cancer or at risk of developing cancer. Some embodiments of the invention may comprise a composition comprising a plurality of particles comprising a platinum(IV) therapeutically active precursor.
1. A composition for delivery of a hydrophilic drug, comprising:
a plurality of particles comprising a hydrophobic interior;
having encapsulated therein a hydrophobic drug precursor comprising a substantially hydrophilic small molecule drug having bound thereto a compatibilizing moiety, in an amount of at least 0.1% by weight based on the weight of the particles.
2. The composition of claim 1 , wherein at least some of the particles further comprise at least one targeting moiety that targets a specific site of delivery in the patient.
3. The composition of claim 1 , wherein the precursor is present in the particle in an amount of at least 0.5% be weight based on the weight of the particles.
4. The composition of claim 1 , wherein the drug precursor comprises an inorganic metal compound and the compatibilizing moiety is a ligand bound to a metal of the inorganic compound.
5. The composition of claim 1 , wherein the drug comprises a platinum metal compound.
6. The composition of claim 5 , wherein the drug comprises a platinum (IV) compound.
7. The composition of claim 5 , wherein the drug comprises a platinum(II) compound.
8. The composition of claim 6 , wherein the platinum (IV) compound comprises the formula
wherein,
R 1 , R 2 , R 3 , and R 4 can be the same or different and each is a group comprising at least one of ammonia, an amine, a heterocycle including at least one nitrogen, an aryl group, or a leaving group, any being optionally substituted, or any two or three of R 1 , R 2 , R 3 , and R 4 can be joined together to form a bidentate ligand or a tridentate ligand, any being optionally substituted, and
R 5 and R 6 can be the same or different and comprise the formula -QR 7 , wherein R 7 is an alkyl, an alkenyl, an alkynyl, a heteroalkyl, a heteroalkynyl, an aryl, a heteroaryl, or CO(CH 2 ) n CH 3 , wherein n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and Q is O or N.
9. The composition of claim 8 , wherein R 7 is CO(CH 2 ) n CH 3 , wherein n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
10. The composition of claim 1 , wherein the compatibilizing moiety comprises at least one of an alkyl, a cycloalkyl, an aryl, or an arylalkyl group.
11. The composition of claim 1 , wherein the particles are polymeric particles.
12. The composition of claim 11 , wherein the polymer comprises poly(D,L-lactic-co-glycolic acid).
13. The composition of claim 2 , wherein the targeting moiety is prostate membrane specific antigen.
14. The composition of claim 2 , wherein the targeting moieties are located on the exterior of the particles.
15. The composition of claim 1 , wherein the drug or drug precursor has a molecular weight of not more than about 800 g/mol.
16. The composition of claim 7 , wherein the platinum(IV) compound is
17. The composition of claim 1 , wherein the particles have an average diameter of not more than about 200 nm.
18. The composition of claim 1 , wherein the particles have an average diameter of at least about 10 nm.
19. The composition of claim 5 , wherein the platinum metal compound is selected from the group consisting of cisplatin, carboplatin, oxaliplatin, [cis-Pt(diaminocyclohexane)Cl 2 ], nedaplatin, stratoplatin, paraplatin, platinol, cycloplatin, dexormaplatin, enloplatin, iproplatin, lobaplatin, ormaplatin, spiroplatin, and zeniplatin.
20. The composition of claim 1 , wherein the drug is selected from the group consisting of dexamethasone phosphate, nicardipine hydrochloride, methylsalicylic acid, nitroglycerine, hydrophilic serotonin 5-HT3 receptor antagonists, and anthracyclines.
21. The composition of claim 1 , comprising inorganic or organometallic drugs selected from the group consisting of platinum compounds, ruthenium compounds, cobalt compounds, copper compounds, and iron compounds.