Evaluation of the potential of nanostructured lipid carriers containing doxycycline functionalized with anti-beta-amyloid protein antibody for intranasal administration in the treatment of Alzheimer's Disease

• Grant number: 23/04282-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2023
• Status: Discontinued
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Maria Palmira Daflon Gremião
• Grantee: Mariana Conceição
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 24/13159-2 - Anti-aggregative activity of doxycycline hyclate loaded-nanostructured lipid carriers against neurodegeneration-related pathogenic proteins, BE.EP.DD

Abstract

Alzheimer's disease (AD), the neurodegenerative disorder with the highest prevalence among cases of dementia in the world, is characterized by functional and cognitive decline, with emphasis on memory loss. The current treatment involves acetylcholinesterase inhibitors that causes significant adverse effects such as nausea, vomiting and liver toxicity. Thus, alternatives to the treatment of AD such as drug repositioning are sought. Doxycycline is an antibiotic that has shown potential in the treatment of AD due to its action on ²-amyloid plaques, which are observed in abundance in patients with AD, decreasing neuronal death and presenting neuroprotective effects with anti-inflammatory and antioxidant activities. AD treatment can also be improved by the intranasal administration of the drug, which is readily absorbed due to the high permeability of the nasal mucosa, being incorporated by the endings of the olfactory and trigeminal nerves that transport molecules directly to the Central Nervous System through the olfactory bulb pathway, thus avoiding hepatic metabolism and interaction with the blood-brain barrier. The encapsulation of the drug in nanostructures such as nanostructured lipid carriers (CLNs) allows greater amounts of active molecules load and sustained release. Such carriers can be functionalized with antibodies, directing the drug to the site of action. Thus, this project proposes to evaluate the encapsulation of doxycycline in CLNs functionalized with anti-²-amyloid protein antibodies for intranasal administration in the treatment of AD, using in vitro (SH-SY5Y lineage neuroblastoma cells) and in vivo (Swiss mice) models, performing behavioral, histological and biochemical analyzes to verify the potential action of the proposed formulation. Through partnerships with different research groups in Brazil and abroad, the project aims to find an effective alternative to the treatment of AD in the developed system. (AU)

Scientific publications

(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)

CONCEICAO, MARIANA; FILIPPO, LEONARDO DELELLO DI; DUARTE, JONATAS LOBATO; BESERRA, FERNANDO PEREIRA; GREMIAO, MARIA PALMIRA DAFLON; CHORILLI, MARLUS. Repurposing doxycycline for Alzheimer's treatment: Challenges from a nano-based drug delivery perspective. BRAIN, BEHAVIOR, & IMMUNITY - HEALTH, v. 42, p. 9-pg., 2024-10-30. (23/04282-2)