Development and in vitro biological evaluation of nanoemulsions containing doxycycline for intranasal administration with potential application in the treatment of Alzheimer's disease

• Grant number: 24/07010-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Gabriela Braga Barros Nhani
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 25/07062-9 - In vitro biological potential of doxycycline loaded- nanoemulsions: anti-aggregative effects on pathogenic proteins related to neurogenerative diseases, BE.EP.MS

Abstract

Alzheimer's disease (AD) is characterized by a progressive cognitive decline and represents a significant concern for public health worldwide, predominating as the leading cause of dementia among the elderly and encompassing 60 to 80% of all dementia cases worldwide. Current pharmacological therapies act only on symptoms, leaving gaps in the effective treatment of the condition, which motivates the search for new therapeutic approaches. The etiological complexity of AD, which involves genetic predispositions and comorbidities, along with the pathological characteristics of ¿-amyloid peptide and tau protein aggregation, highlights the need for more efficient therapies. Doxycycline (DOX), in both its hyclate (DOXI) and hydrochloride (C-DOX) forms, an antibiotic with the ability to cross physiological barriers and extensively proven neuroprotective action, is emerging as a promising candidate for repositioning as a treatment for AD, offering a less expensive and faster option compared to the development of new drugs. Thus, this project aims to obtain and characterize nanoemulsions containing DOXI for intranasal administration, exploring its potential as an innovative treatment for AD. The preparation of nanoemulsions will be carried out by lipid selection and surfactant-assisted formation, followed by characterization of the formulations in terms of mean hydrodynamic diameter, polydispersity index, zeta potential and morphology, using techniques such as dynamic light scattering, electrophoretic mobility and transmission electron microscopy. The stability of the nanoemulsions and the controlled release of doxycycline will be evaluated under various storage conditions. In vitro tests to determine the cytotoxicity and biological efficacy of the chitosan-coated nanoemulsions against A¿1-42 proteins will complement the study to confirm the feasibility and efficacy of the proposed therapeutic approach.