Add time:08/01/2019         Source:sciencedirect.com

Small molecule retinoids are potential therapeutics for a variety of neurological diseases. However, most retinoids are poorly water soluble and difficult to deliver in vivo, which prevents further study of their utility to treat disease. Here, we focus on Adapalene (cas 106685-40-9), an FDA approved drug that is a specific agonist for the retinoic acid receptor β (RARβ). We sought to develop nanoparticle delivery systems that would enable effective delivery of adapalene to the CNS. We developed strategies to produce nanoparticles based on the hypothesis that incorporation of hydrophobic molecules into a polyester base would improve adapalene loading. In the first scheme, poly (lactic acid)-poly (ethylene glycol) (PLA-PEG) was blended with low molecular weight poly (lactic acid) (PLA) or poly (caprolactone) (PCL). In the second scheme, poly (lactic-co-glycolic acid) (PLGA) was blended with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol) (DSPE-PEG). Our data demonstrate that blending low molecular weight polyesters or DSPE-PEG into the primary nanoparticle base improves encapsulation of adapalene, presumably by enhancing adapalene solubility in the nanoparticle. Peripheral administration of these nanoparticles activated retinoid signaling in the brain and spinal cord of healthy mice. These studies provide new approaches for nanoparticle fabrication and establish proof of principle that systemically administered, adapalene-loaded nanoparticles activate retinoid signaling in the CNS.

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