(214e) Dendrimer-Based Nanodevices for Sustained Intravitreal Drug Delivery

Authors: 
Raja Guru, B., Wayne State University
Iezzi, R., Mayo Clinic


Neurodegenerative diseases such as retinitis pigmentosa and age related macular degeneration are due to degeneration of photoreceptor cells of retina. Though some of the neuroprotective drugs like fluocinolone acetonide (FA) are available for treatment, it is difficult to deliver therapeutic amount of drug to the diseased site for a sustained period. We have developed polyamidoamine (PAMAM) dendrimer based nanodevices (size °Ö5 nm) for sustained delivery of neuroprotectants. A single intravitreal injection of the nanodevice appears to prevent the neurodegeneration up to one month in RCS rats, in vivo model used for this project. These were based on both electroretinography and cell count measurements. In vivo biodistribution measurements of FITC-labeled PAMAM dendrimers suggested that dendrimers localized in the activated microglial cells and astrocytes. To understand the release of drug from the dendrimer nanodevices, we conducted in vitro release of drug from the nanodevice at different pH conditions.

To enable sustained delivery for 6 months from a single intravitreal injection, we encapsulated these nanodevices in to a microparticle made up of FDA approved biomaterial which can release drug-dendrimer nanodevice for longer period. In vitro release profile of the nanodevices from the microparticles at different pH conditions have been found out and the stability of the drug-dendrimer nanodevices inside the microparticles have been analyzed. We will present results of in vivo efficacy of drug-dendrimer nanodevices, biodistribution of fluorescently-labeled dendrimers in diseased rats and healthy rats, in vitro release profile of drug from dendrimer nanodevice and in vitro release profile of drug-dendrimer nanodevice from the microparticle.