Hydroxypropyl-β-cyclodextrin formulated in nasal chitosan microspheres as candidate therapeutic agent in Alzheimer's disease

Hydroxypropyl-β-cyclodextrin (HP-CD) is a hydroxyalkyl derivative of native β-cyclodextrin, cyclic oligosaccharide able to form inclusion complexes with many drugs and biomolecules [1]. Cyclodextrins have a possible neuroprotective effect due to their capability to extract and deplete cholesterol from cell membranes [1]. HP-CD is classified as an excipient (cyclodextrins are in fact widely used to improve solubility of poorly water soluble drugs) and it is not been FDA-approved as therapeutic agent. However HP-CD received the "orphan drug designation" in the United States and Europe because it is employed in individual compassionate use for patients suffering from Niemann-Pick type C. This is a fatal neurological disease characterized by an abnormal storage of cholesterol within the cells and in particular nervous cells causing neurodegeneration [2]. Elevated cholesterol levels produce also the accumulation of beta-amyloid (Aβ) in cellular systems and several animal models of Alzheimer's disease (AD) [3]. AD is a chronic neurodegenerative disease which affects nearly 44 million people worldwide and the global cost of Alzheimer's disease and dementia is estimated to be $605 billion [4]. Cholesterol depletion, disruption or inhibition of Aβ aggregation are possible therapeutic approaches of AD.