Dendrimer based nanodevices for therapeutic and imaging purposes
A nanodevice composition including N-acetyl cysteine linked to a dendrimer, such as a PAMAM dendrimer or a multiarm PEG polymer, is provided. Also provided is a nanodevice for targeted delivery of a compound to a location in need of treatment. The nanodevice includes a PAMAM dendrimer or multiarm PEG polymer, linked to the compound via a disulfide bond. There is provided a nanodevice composition for localizing and delivering therapeutically active agents, the nanodevice includes a PAMAM dendrimer or multiarm PEG polymer and at least one therapeutically active agent attached to the PAMAM dendrimer or multiarm PEG polymer. A method of site-specific delivery of a therapeutically active agent, by attaching a therapeutically active agent to a PAMAM dendrimer or multiarm PEG polymer using a disulfide bond, administering the PAMAM dendrimer or multiarm PEG polymer to a patient in need of treatment, localizing the dendrimer or multiarm PEG polymer to a site in need of treatment, and releasing the therapeutically active agent at the site in need of treatment.
1. A composition comprising a polyamidoamine (PAMAM) dendrimer linked to N-acetyl cysteine, optionally via one or more spacers.
2. The composition of claim 1 , wherein the PAMAM dendrimer is a generation 3, generation 4, generation 5, generation 6, generation 7, generation 8, generation 9, or generation 10 PAMAM dendrimer.
3. The composition of claim 2 , wherein the PAMAM dendrimer is a generation 4 PAMAM dendrimer.
4. The composition of claim 3 , wherein the generation 4 PAMAM dendrimer has one or more terminal functional groups selected from the group consisting of carboxylic, amine, and hydroxyl groups.
5. The composition of claim 1 , wherein the dendrimer is linked to N-acetyl cysteine via one or more spacers.
6. The composition of claim 5 , wherein the one or more spacers are selected from the group consisting of N-Succinimidyl 3-(2-pyridyldithio)-propionate, Glutathione, Gamma-aminobutyric acid, and combinations thereof.
7. The composition of claim 1 , wherein the dendrimer is linked to N-acetyl cysteine via disulfide bonds.
8. The composition of claim 1 , wherein the composition is in an amount effective to treat inflammation or neuroinflammation in a subject in need thereof.
9. The composition of claim 1 , wherein the composition is in an amount effective for targeting to activated microglia and astrocytes of the central nervous system.
10. The composition of claim 1 , wherein the composition is in an amount effective to reduce the level of hydrogen peroxide, and/or nitrite in activated microglia and astrocytes of the central nervous system.
11. The composition of claim 1 , wherein the composition is in an amount effective to treat and or prevent one or more symptoms of cerebral palsy or white matter injury in the brain.
12. The composition of claim 1 formulated for parenteral, topical or oral administration.
13. The composition of claim 1 formulated in a form selected from the group consisting of hydrogels, nanoparticle or microparticles, suspensions, gels, ointments, powders, tablets, capsules and solutions.
14. A method of reducing or preventing inflammation comprises administering an effective amount of composition according to claim 1 .
15. The method of claim 14 , wherein the inflammation is chronic inflammation associated with heart attack, Alzheimer's disease, congestive heart failure, stroke, arthritis, aortic valve stenosis, kidney failure, lupus, asthma, psoriasis, pancreatitis, allergies, fibrosis, surgical complications, anemia, fibromyalgia, or combinations thereof.
16. The method of claim 14 , wherein the inflammation is neuroinflammation.
17. The method of claim 16 , wherein the neuroinflammation has pathogenesis associated with activated microglia and/or astrocytes.
18. The method of claim 16 , wherein the neuroinflammation is associated with cerebral palsy.
19. A method of reducing or preventing microbial growth in a subject in need thereof comprising administering an effective amount of the composition according to claim 1 .
20. The method of claim 19 , wherein the method of reducing or preventing microbial growth comprises administering via a route selected from the group consisting of vaginal, cervical, and rectal routes.