DEVELOPMENT OF LIQUID CRYSTALLINE NANOPARTICLES FOR CO-DELIVERY OF DRUG AND siRNA IN ALZHEIMER'S DISEASE THERAPY

• Grant number: 25/01771-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2025
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Maria Vitória Lopes Badra Bentley
• Grantee: João Vitor de Almeida Pereira
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach, AP.TEM

Abstract

Dementia is a neurological syndrome involving irreversible cognitive decline characterized by progressive memory loss and other symptoms. The main manifestation of the syndrome is Alzheimer's disease (AD), which is characterized by memory loss and the accumulation of senile plaques. Current treatment aims to delay symptoms through the administration of acetylcholinesterase inhibitors and NMDA antagonists. Since there is no cure and the etiology is still unknown, great efforts have been made to develop new technologies to improve its treatment. Gene silencing therapy and the use of new drugs are examples of these approaches. Piperine is an alkaloid derived from Piper nigrum that has, among other therapeutic effects, anti-neurodegenerative and neuroprotective activity. BACE1 siRNA is a silencing nucleotide that has the ability to inhibit the translation of the ¿-secretase protein, responsible for the origin of senile plaques. However, the co-administration of these two therapeutic agents presents pharmacotechnical challenges related to the different physicochemical characteristics of these drugs, stability in biological media and adequate delivery to the target site, in this case the brain where drug release is limited by the blood-brain barrier. Nanotechnological solutions, such as liquid crystal nanoparticles, are explored to optimize the co-delivery of drugs and siRNA and can overcome the main barrier for the delivery of these drugs to the brain, the blood-brain barrier. Thus, this work aims to develop liquid crystalline nanoparticles, specifically cubic phase, that enable the intravenous co-administration of piperine and siRNA BACE 1, as an alternative for AD therapy. In this sense, the careful selection of the structural components and surface modifiers of the liquid crystalline nanoparticles, the process of obtaining and in vitro evaluation will be challenges for the present proposal and will be achieved through adequate experimental design. (AU)