Abstract
Pioglitazone has been reported in the literature to have a substantial role in the improvement of overall cognition in a mouse model. With this in mind, the aim of this study was to determine the most efficacious route for the administration of Pioglitazone nanoparticles (PGZ-NPs) in order to promote drug delivery to the brain for the treatment of Alzheimer’s disease. PGZ-loaded NPs were developed by the solvent displacement method. Parameters such as mean size, polydispersity index, zeta potential, encapsulation efficacy, rheological behavior, and short-term stability were evaluated. Ex vivo permeation studies were then carried out using buccal, sublingual, nasal, and intestinal mucosa. PGZ-NPs with a size around of 160 nm showed high permeability in all mucosae. However, the permeation and prediction parameters revealed that lag-time and vehicle/tissue partition coefficient of nasal mucosa were significantly lower than other studied mucosae, while the diffusion coefficient and theoretical steady-state plasma concentration of the drug were higher, providing biopharmaceutical results that reveal more favorable PGZ permeation through the nasal mucosa. The results suggest that nasal mucosa represents an attractive and non-invasive pathway for PGZ-NPs administration to the brain since the drug permeation was demonstrated to be more favorable in this tissue.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is considered the most common cause of dementia [1,2]
The formulation of Pioglitazone nanoparticles (PGZ-NPs) consists of two phases: the first is composed of the drug, dimethyl sulfoxide (DMSO), and acetone while the second phase consists of Tw 80 and water
The PGZ-NPs showed a size around 160.0 ± 1.3 nm with polydispersity index (PI) values in the range of monodisperse systems (PI < 0.1) and high association efficiency (≈92%)
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is considered the most common cause of dementia [1,2]. Chronic neuroinflammation has been described as a pathological feature which may contribute to amyloid plaque progression and neurodegeneration [5,6]. PPAR-γ is a nuclear receptor whose activation regulates genes involved in glucose homeostasis, lipid metabolism, and inflammation [7,8,9]. Recent studies have shown that PPAR-γ ligands inhibit proinflammatory gene expression, regulate amyloidogenic pathways, and exhibit neuroprotective effects [10,11,12]. Pioglitazone (PGZ) is a PPAR-γ activator that increases tissue sensitivity to insulin and is widely used to treat type 2 diabetes mellitus (T2DM) [13]. Other pharmacological effects reported for PGZ include selective suppression of the T-helper 17 (Th17) cells differentiation and improvements in Polymers 2018, 10, 316; doi:10.3390/polym10030316 www.mdpi.com/journal/polymers
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