Combined Donepezil with Astaxanthin via Nanostructured Lipid Carriers Effective Delivery to Brain for Alzheimer's Disease in Rat Model.

Introduction: Donepezil (DPL), a specific acetylcholinesterase inhibitor, is used as a first-line treatment to improve cognitive deficits in Alzheimer's disease (AD) and it might have a disease modifying effect. Astaxanthin (AST) is a natural potent antioxidant with neuroprotective, anti-amyloidogenic, anti-apoptotic, and anti-inflammatory effects. This study aimed to prepare nanostructured lipid carriers (NLCs) co-loaded with donepezil and astaxanthin (DPL/AST-NLCs) and evaluate their in vivo efficacy in an AD-like rat model 30 days after daily intranasal administration.

Nose to Brain Delivery of Astaxanthin-Loaded Nanostructured Lipid Carriers in Rat Model of Alzheimer's Disease: Preparation, in vitro and in vivo Evaluation.

Background: Astaxanthin (AST) is a second-generation antioxidant with anti-inflammatory and neuroprotective properties and could be a promising candidate for Alzheimer's disease (AD) therapy, but is shows poor oral bioavailability due to its high lipophilicity.

Purpose: This study aimed to prepare and evaluate AST-loaded nanostructured lipid carriers (NLCs), for enhanced nose-to-brain drug delivery to improve its therapeutic efficacy in rat model of AD.

Methods: AST-NLCs were prepared using hot high-pressure homogenization technique, and processing parameters such as total lipid-to-drug ratio, solid lipid-to-liquid lipid ratio, and concentration of surfactant were optimized.