Dendrimers for sustained release of compounds
Dendrimer-based compositions and methods are provided, that are useful for administering pharmaceutical compositions to target cells and tissues for treatment of ocular diseases including macular degeneration, diabetic retinopathy, and retinitis pigmentosa.
1. A method of treating microglia or macrophage-mediated ocular neuroinflammation in a subject in need thereof, the method comprising:
intravitreally administering to the subject a dendrimer-drug conjugate comprising a generation 4 (G4) polyamidoamine (PAMAM) dendrimer with free hydroxyl terminal groups and one or more biologically active agents conjugated thereto, wherein the inflammation is caused by a disease or disorder of the retina,
wherein the dendrimer-drug conjugate is selectively taken up by activated microglial cells or macrophages at a site of ocular neuroinflammation, and
wherein the dendrimer-drug conjugate is in an amount effective to provide sustained release of the one or more biologically active agents for at least one month at the site of ocular neuroinflammation.
2. The method of claim 1 , wherein the disease or disorder of the retina is selected from the group consisting of retinitis pigmentosa, age-related macular degeneration (AMD), atrophic AMD, retinal detachment, retinal ischemia, arteriosclerotic retinopathy, hypertensive retinopathy, retinal artery blockage, retinal vein blockage, diabetic retinopathy, and macular edema.
3. The method of claim 1 , wherein the biologically active agent is selected from the group consisting of neurostimulants and neuroprotectants.
4. The method of claim 1 , wherein the biologically active agent is selected from the group consisting of pegaptanib, anecortave acetate, and Combretastatin A4 prodrug.
5. The method of claim 1 , wherein the biologically active agent is conjugated to the hydroxyl terminal group via an ester bond.
6. The method of claim 1 , wherein the dendrimer and the one or more biologically active agents conjugated thereto are encapsulated in a nanoparticle.
7. The method of claim 1 , wherein the dendrimer is not conjugated to a targeting moiety.