Abstract
Tackling Neurodegeneration with By-Product-Based Nanohydrogels for the Nose-to-Brain Delivery of Natural Bioactive Compounds (Acronym: TANDEM) The TANDEM project proposes an innovative, multidisciplinary approach to addressing neurodegenerative diseases—such as Alzheimer’s, Parkinson’s, and multiple sclerosis—through the development of a novel, sustainable nanomedicine system. The project leverages bioconjugates made from sericin, a silk industry by-product, and hyaluronic acid to create nanohydrogels (NGs) capable of encapsulating and delivering neuroprotective natural bioactive compounds (NBCs), specifically sulforaphane (SFN) and isoliquiritigenin (ILQ), via intranasal administration. This strategy aims to bypass the blood-brain barrier (BBB), a major obstacle in central nervous system (CNS) drug delivery. The overarching goal of TANDEM is to develop a sustainable, biocompatible, and effective delivery system for neuroprotective agents targeting the brain. The key scientific objectives are: • Develop green extraction and purification processes for sericin from textile industry by-products, emphasizing sustainability and molecular integrity. • Synthesize and characterize a novel sericin-hyaluronic acid (or sericin-chitosan) bioconjugate using green chemistry, optimizing gelation, rheology, and degradation profiles. • Design and produce mucoadhesive, chemically stabilized nanohydrogels tailored for nasal-to-brain delivery using a Quality-by-Design (QbD) and Design of Experiment (DoE) approach. • Evaluate the neuroprotective, anti-inflammatory, and anti-ageing effects of NGs in vitro using microglia (BV-2), neuron-like SH-SY5Y, and astrocyte models. • Confirm therapeutic efficacy of NGs in vivo in two murine models of multiple sclerosis: PLP-induced EAE in SJL mice (relapsing-remitting form) and MOG-induced EAE in C57BL/6 mice (progressive form). The project includes both basic and applied research involving: 1. Extraction & Functionalization: Sericin is extracted using ultrasonic techniques (a green process), then functionalized with vinylsulfone groups. It is conjugated with thiolated hyaluronic acid or chitosan to obtain amphiphilic biopolymers. 2. Nanohydrogel Design: Two fabrication methods will bw used—one based on emulsification and one solvent-free aqueous method using ionic interactions and cross-linkers such as polylysine. NGs are loaded with SFN and ILQ either via co-delivery or dual-delivery schemes. 3. In Vitro Evaluation: o Anti-inflammatory potential is tested in BV-2 microglia activated with LPS. o Neuroprotection is evaluated in co-culture with differentiated SH-SY5Y neurons. o Anti-ageing effect is analyzed in astrocytes and glioblastoma lines after induced senescence using oxidative stress or low-glucose conditions. 4. In Vivo Studies: NGs will be administered intranasally to mice models with EAE. Disease progression, cytokine levels, antigen-specific T cell proliferation, and histological markers in CNS tissue are analyzed. Expected Results • Technological Outcomes: Development of novel, biodegradable, and mucoadhesive NGs capable of CNS targeting via nasal administration. • Biological Outcomes: Demonstration of enhanced anti-inflammatory, antioxidant, and neuroprotective properties of NG-encapsulated SFN and ILQ in vitro and in vivo. • Therapeutic Impact: Identification of effective NG-based treatments capable of slowing or preventing neurodegeneration with high biocompatibility and patient compliance. • Sustainability Outcomes: Valorization of sericin, a low-value by-product, via a circular economy model; promotion of environmentally responsible production practices. TANDEM is a joint effort among four Italian universities: Università degli Studi “G. d’Annunzio” Chieti-Pescara (PI: Prof. Piera Di Martino), Università di Camerino (Prof. Roberta Censi), Università di Bologna (Prof. Cristina Angeloni), and Università di Catania (Prof. Ter
Project details
Unibo Team Leader: Cristina Angeloni
Unibo involved Department/s:
Dipartimento di Scienze per la Qualità della Vita
Coordinator:
Università degli Studi G.D'Annunzio di Chieti - Pescara(Italy)
Total Unibo Contribution: Euro (EUR) 48.692,00
Project Duration in months: 24
Start Date:
28/09/2023
End Date:
28/02/2026
