Intranasal delivery of dopamine to the striatum using glycol chitosan/sulfobutylether-β-cyclodextrin based nanoparticles

Abstract

The aim of this study was to evaluate chitosan (CS)-, glycol chitosan (GCS)- and corresponding thiomer-based nanoparticles (NPs) for delivering dopamine (DA) to the brain by nasal route. Thus, the polyanions tripolyphosphate and sulfobutylether-β-cyclodextrin (SBE-β-CD), respectively, were used as polycation crosslinking agents and SBE-β-CD also in order to enhance the DA stability. The most interesting formulation, containing GCS and SBE-β-CD, was denoted as DA GCS/DA-CD NPs. NMR spectroscopy demonstrated an inclusion complex formation between SBE-β-CD and DA. X-ray photoelectron spectroscopy analysis revealed the presence of DA on the external surface of NPs. DA GCS/DA-CD NPs showed cytotoxic effect toward Olfactory Ensheathing Cells only at higher dosage. Acute administration of DA GCS/DA-CD NPs into the right nostril of rats did not modify the levels of the neurotransmitter in both right and left striatum. Conversely, repeated intranasal administration of DA GCS/DA-CD NPs into the right nostril significantly increased DA in the ipsilateral striatum. Fluorescent microscopy of olfactory bulb after acute administration of DA fluorescent-labeled GCS/DA-CD NPs into the right nostril showed the presence of NPs only in the right olfactory bulb and no morphological tissue damage occurred. Thus, these GCS based NPs could be potentially used as carriers for nose-to-brain DA delivery for the Parkinson's disease treatment.

Keywords: Brain delivery; Chitosan (PubMed CID: 71853); Chitosan/glycol chitosan; Dihydroxyphenylacetic acid (PubMed CID: 547); Dopamine; Dopamine hydrochloride (PubMed CID: 65340); Fluorescein isothiocyanate (PubMed CID: 18730); Nanoparticles; Nasal administration; Noradrenaline (PubMed CID: 439260); Pentasodium tripolyphosphate (PubMed CID: 24455); XPS (X-ray photoelectron spectroscopy); l-Dopa (PubMed CID: 6047); β-Cyclodextrin (PubMed CID: 444041).