In vitro biological potential of doxycycline loaded- nanoemulsions: anti-aggregative effects on pathogenic proteins related to neurogenerative diseases

• Grant number: 25/07062-9
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: September 02, 2025
• End date: February 01, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Gabriela Braga Barros Nhani
• Supervisor: Tiago Fleming de Oliveira Outeiro
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: University Medical Center Göttingen, Germany
• Associated to the scholarship: 24/07010-6 - Development and in vitro biological evaluation of nanoemulsions containing doxycycline for intranasal administration with potential application in the treatment of Alzheimer's disease, BP.MS

Abstract

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's,share the common feature of pathological protein aggregation that becomes toxic to braintissue, leading to cell death. While in Alzheimer's, beta-amyloid (¿A) and Tau proteinsaggregate in insoluble amyloid plaques and neurofibrillary tangles, in Parkinson'sdisease (PD) alpha-synuclein (aSyn), a presynaptic neuronal protein is the one toprovoke degeneration through a prion mechanism. Doxycycline, a second-generationtetracycline antibiotic, showed in vitro and in vivo anti-aggregative activity against ¿A,Tau and aSyn. It represents a promising molecule to be applied to Alzheimer's andParkinson's diseases as it prevents the formation of protein aggregates and disrupts thealready formed ones. Aiming at a repurposed use of doxycycline againstneurodegeneration in a nanotechnological approach, this research intends to evaluatedoxycycline's anti-aggregation capacity when loaded by nanoemulsions. These are lipidnanoparticles whose size and constitution allow improved ability to reach brain areas. The research, aSyn, will be tested with doxycycline-free or loaded nanoemulsion tounderstand whether the nanoparticles can improve aggregate disruption and prevent itsformation. The analysis includes cell-free assays such as Thioflavin T, immunoblotting,dynamic light scattering, and fluorescence analysis to assess aSyn aggregation, and cell-based ones, such as immunocytochemistry, cytotoxicity with H4 and HEK293, andmicroscopy.