Poly(ethyl cyanoacrylate) nanoparticles for brain delivery of andrographolide

The limitations imposed by the blood-brain barrier (BBB) and the non-selective distribution of drugs in the brain have hindered the effective treatment of brain diseases and may result in severe side effects on the normal brains. The aim of this work was to deliver natural molecules into nanoparticles capable to provide sustained and controlled drug release, improved biodistribution and therapeutic efficacy for Alzheimer's Disease (AD) prevention and therapy. Novel fluorescent polymeric nanoparticles to target brain tissues were designed and optimised to follow their in vivo distribution as new strategies to cross the BBB, namely ethylcyanoacrylate nanospheres (ECA-NSs) coated with polysorbate 80. They were prepared by emulsion polymerization method using fluorescein isothiocyanate linked to dextran as a florescent probe. NSs were characterized in terms of dimension, polydispersity, zeta potential, morphology, encapsulation efficacy, loading capacity and stability of probe by DLS, TEM and HPLC-DAD-FLD, respectively. A study after intracerebral injection of nanoparticles in nucleus basalis magnocellularis of rats, colynergic neuronal location, evidenced that NSs did not induce inflammatory response. NSs were also administered intraperitoneally and intravenously to anaesthetized rats to evaluate their biodistribution by fluorescent microscope images. The biodistribution studies revealed that NSs were able to cross the BBB and reach brain tissue, as a consequence they were loaded with andrographolide, a major diterpenoid ofAndrographis paniculata (Burm. f.) Nees, whose clinical utility for the treatment of inflammation-related neurodegenerative disorder has been demonstrated. ECA-NSs were produced with good yields, suitable for the intraperitoneally administration (mean diameter ≤300nm; PDI 0.2), with a sphere-like shape and a good encapsulation efficacy. The developed nanocarriers represent a valuable targeting system for AD therapy.