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

Grant number: 15/05394-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2016
Effective date (End): March 31, 2019
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal researcher:Marlus Chorilli
Grantee:Bruno da Fonseca dos Santos
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated scholarship(s):18/10760-6 - Pharmaceutical technology for the solubility improvement of trans-resveratrol and its application for designing of muco(bio)adhesive formulations, BE.EP.DR


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)

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Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FONSECA-SANTOS, BRUNO; DOS SANTOS, ALINE MARTINS; RODERO, CAMILA FERNANDA; DAFLON GREMIAO, MARIA PALMIRA; CHORILLI, MARLUS. Design, characterization, and biological evaluation of curcumin-loaded surfactant-based systems for topical drug delivery. INTERNATIONAL JOURNAL OF NANOMEDICINE, v. 11, p. 4553-4562, . (15/05394-2, 13/03746-3)
FONSECA-SANTOS, BRUNO; CHORILLI, MARLUS. An overview of polymeric dosage forms in buccal drug delivery: State of art, design of formulations and their in vivo performance evaluation. Materials Science & Engineering C-Materials for Biological Applications, v. 86, p. 129-143, . (15/05394-2, 13/03746-3)
FONSECA-SANTOS, BRUNO; CHORILLI, MARLUS. The uses of resveratrol for neurological diseases treatment and insights for nanotechnology based-drug delivery systems. International Journal of Pharmaceutics, v. 589, . (15/05394-2, 14/24180-0, 12/19568-4)
FONSECA-SANTOS, BRUNO; SILVA, PATRICIA BENTO; RIGON, ROBERTA BALASIN; SATO, MARIANA RILLO; CHORILLI, MARIUS. Formulating SLN and NLC as Innovative Drug Delivery Systems for Non-Invasive Routes of Drug Administration. Current Medicinal Chemistry, v. 27, n. 22, p. 3623-3656, . (13/09265-7, 16/11198-4, 15/05394-2, 14/24180-0, 13/21500-1)
FONSECA-SANTOS, BRUNO; CHORILLI, MARLUS. An overview of carboxymethyl derivatives of chitosan: Their use as biomaterials and drug delivery systems. Materials Science & Engineering C-Materials for Biological Applications, v. 77, p. 1349-1362, . (15/05394-2, 14/24180-0)
DE ARAUJO, PATRICIA ROCHA; FONSECA-SANTOS, BRUNO; KOGAWA, ANA CAROLINA; NUNES SALGADO, HERIDA REGINA; CHORILLI, MARLUS. A Review of Analytical Methods for the Determination of Hypericin in Foods, Herbal, Biological and Pharmaceutical Matrices. CURRENT PHARMACEUTICAL DESIGN, v. 26, n. 36, p. 4648-4657, . (15/05394-2)

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