Idebenone-Loaded Nanocomposite Microspheres for Nasal Administration-A Perspective in the Treatment of Alzheimer's Disease.

Abstract

Background: Alzheimer's disease results in neurodegeneration and is characterized by an accumulation of abnormal neuritic lesions and intracellular aggregates of hyperphosphorylated Tau proteins in the cerebrum. That leads to progressive decline in memory, thinking, and learning skills. Oxidative stress has been shown to play a significant role in the pathogenesis of Alzheimer's disease. Antioxidants are identified as part of therapeutic strategy to prevent or reduce the disease. Idebenone is a synthetic analogue of coenzyme Q₁₀ with potent antioxidant properties, originally developed for the treatment of Alzheimer's disease and other cognitive disorders. After oral administration idebenone undergoes excessive first-pass metabolism and has a very low bioavailability of only about 1%. The use of an alternative route of administration such as the nasal and its incorporation into a novel carrier (nanocomposite microspheres) will eliminate the problems associated with reduced absorption, stability, and rapid biotransformation and will increase the opportunity for idebenone to realize its therapeutic potential in Alzheimer's disease.

Methods: Idebenone-loaded nanocomposite microspheres were obtained by spray drying. The structures were characterized using laser diffraction, scanning electron microscopy, high-performance liquid chromatography, Fourier-transform infrared spectroscopy, and differential scanning calorimetry. The ability of nanocomposite microspheres to bind human serum albumin was investigated by fluorescence spectroscopy. The mucoadhesive properties of the carrier were also determined.

Results: Bioadhesive nanocomposite microparticles with spherical shape, smooth surface, size of 7.37 ± 2.4 μm, and with high production yield, good drug entrapment efficiency, and loading values were obtained. Infrared spectra demonstrated no chemical interactions between idebenone and structure-forming polymers. The ability of particles to bind to human serum albumin depends on their drug loading.

Conclusions: Nanocomposite microspheres were developed as the novel delivery system of idebenone for target nose-to-brain delivery. The obtained carrier may increase the therapeutic potential of idebenone by providing higher concentrations in brain tissue and reducing systemic exposure and side effects.