Evaluating the potential of nanostructured surfactant-based systems to intranasal administration of trans-resveratrol in the optimization of Alzheimer's disease therapy

Abstract

Alzheimer's disease (AD) is a highly incident pathology in the world, affecting approximately 40 million of people aged over 65 years, leading to loss of memory and cognition. The current treatment is based on the use of acetylcholinesterase inhibitors that have adverse effects, such as nausea, vomiting, diarrhea and hepatotoxicity. Thus, many researchers are striving in the discovery of substances, including those from natural sources, which it can present therapeutic interest to treat this disease. Trans-resveratrol (RES) has shown activity in treatment of AD, acting on specific molecular pathways, such as the ability to inhibit the formation of amyloid plaque, depolymerization of plaque formed during disease, acting on the cholinergic system, inhibiting acetylcholinesterase, and neuroinflammation, decreasing the formation of free radicals in the brain. However, its clinical use has many challenges because physicochemical characteristics resulting in low bioavailability by the oral route, So, their incorporation into surfactant-based nanostructured systems (SBNS) and alternative routes of administration, such as nasal, show to be an interesting tool. Nasal administration of RES can be advantageous, since the nasal mucosa has a high permeability, high blood supply and absence of first-pass metabolism, by-passing blood-brain barrier, optimizing its action in the central nervous system (CNS) via olfactory-bulb. In spite of advantages of this administration route, there are some barriers could limit the drug absorption, such as mucociliary clearance mechanism that can remove the formulation of the nasal cavity. A strategy to overcome these obstacles is the use of in situ gelling SBNS, since they can increase the contact between the formulation and absorption sites in the nasal cavity, slowing mucociliary clearance, thus increasing the absorption systemic of the RES and its vectorization to the brain. This research aims to design and characterize SBNS, such as microemulsions and liquid crystal systems, consisting of ethoxylated oleyl acid, oleic acid and aqueous phase with and without O-carboxymethyl chitosan to nasal administration of RES and then perform in vitro and in vivo biological activities to evaluate the potential of the formulations in the treatment of AD. (AU)