ADVANCED NANOPARTICLE-BASED MATERIALS WITH SYNERGISTIC EFFECT ON
NEURONAL OXIDATIVE STRESS AND BETA-AMYLOID FIBRILLATION
FOR PREVENTIVE TREATMENT IN ALZHEIMER'S DISEASE - NANONERVES

DESCRIPTION

Finacing: State budget
Programme: PNCDI III-Program 2: Increasing the competitiveness of the Romanian economy through research, development and innovation, Demonstration experimental project (PED)
Project code: PN-III-P2-2.1-PED-2019-4657
Project title: Advanced nanoparticle-based materials with synergistic effect on neuronal oxidative stress and beta-amyloid fibrillation for preventive treatment in Alzheimer's disease (Nanonerves)
Contract No.: 318 PED/2020
Total value: 600000 lei
State budget value: 600000 lei
Project duration: 24 luni
Contract period: 03.08.2020 - 02.08.2022
Contractor: National Research & Development Institute for Chemistry and Petrochemistry - ICECHIM Bucharest
Contracting authority: The Executive Unit for Financing Higher Education, Research, Development and Innovation
Project director: PhD Cristina Lavinia Nistor; e-mail: lc_nistor@yahoo.com; cristina.nistor@icechim-pd.ro


PARTNERS

Coordinator (CO): NATIONAL RESEARCH & DEVELOPMENT INSTITUTE FOR CHEMISTRY AND PETROCHEMISTRY-ICECHIM, 202 Spl. Independentei, Bucharest, tel: 021.315.32.99, fax: 021.312.34.93
Partner (P1): University of Bucharest, tel: 021 307 73 00, fax: 021 313 17 60,


SUMMARY

This project aims to develop and to validate a new product and its technology with application in preventive treatment of Alzheimer's disease. This new product includes bioactive ingredients with effect on neuronal oxidative stress (curcumin) and beta-amyloid fibrillation (Ag and ZnO functionalized nanoparticles), and a nanocarrier (PEG-functionalized silica particles), that can act itself as a beta-amyloid fibrillation inhibitor.


OBJECTIVE

This project aims to develop and to validate a new product and its technology with application in preventive treatment of Alzheimer's disease. This new product includes bioactive ingredients with effect on neuronal oxidative stress (curcumin) and beta-amyloid fibrillation (Ag and ZnO functionalized nanoparticles), and a nanocarrier (PEG-functionalized silica particles), that can act itself as a beta-amyloid fibrillation inhibitor. The main project novelty is related to: (i) study of the interaction of new formulations based on Ag or ZnO NPs and Curcumin encapsulated in functionalized silica NPs with beta amyloid fibrils and (ii) a sistematic and rational scientific approach to strike a balance between the effect of modifying the kinetics of amyloid beta fibril formation and the prevention of toxic effects (otherwise known) on neurons. Project objectives are: (i) to optimize product components and to improve their compatibility; (ii) to develop demonstration model, through components integration and (iii) to test and to validate the demonstration model, on laboratory conditions. Objectives are related to different TRLs: improved compatibility and optimal composition of new formulations based on Ag or ZnO NPs and Curcumin encapsulated in functionalized silica NPs (1st objective) allow properties analysis and improvement (TRL 3). Components integration (2nd objective) and product testing in laboratory conditions (3rd objective) permit technological development up to TRL 4.


STAGE 1/2020 - Preparation and optimization of new types of functionalized metal nanoparticles (NP), of different shapes and dimensions; Physico-chemical characterization of the obtained compounds.
Development period: 03.08.2020-31.12.2020

STAGE 2/2021 - Synthesis and characterization of new formulations for the prevention of beta-amyloid fibrillation, based on NP of Ag or ZnO and curcumin, encapsulated in silica NP.
Development period: 01.01.2021-31.12.2022

STAGE 3/2022 - Process development and validation of the new beta amyloid fibrils inhibiting product.
Development period: 01.01.2022-02.08.2022


RESULTS

REALIZED

• 1 synthesis method to obtain functionalized Ag NPs;
• 1 synthesis method to obtain functionalized ZnO NPs;
• 1 optimized process of preparation of functionalized metallic NPs;
• 1 process to obtain PEG-functionalized silica NPs as a transport vector;
• 1 evaluation report about cell viability, cytotoxicity of doses and exposure intervals of NPs;
• 1 optimized process of preparation of new formulations based on metallic NPs and Curcumin, encapsulated in functionalized silica NPs;
• 1 work protocol for testing the optimized nanosystem;
• 1 functional laboratory model of nanosystem for preventing beta amyloid fibrillation;
• 1 optimized laboratory technology for preparation of an efficient and innovative beta amyloid fibrils inhibiting product;
• 1 work protocol for validation of the functional laboratory model;
• 1 website page to promote the project;
• 1 patent application;
• 1 workshop;
• participation to 9 national/international conferences;
• 3 articles send for publication.

1. C. Scomoroscenco, L.O. Cinteza, R. Ianchis, C.L. Nistor, C. Petcu, C.M. Ninciuleanu, E. Alexandrescu, C.I. Mihaescu, M. Teodorescu, "Curcumin Delivery Systems With Biomedical Applications", 3rd International Conference on Emerging Technologies in Materials Engineering-EmergeMAT, Bucharest, Romania, 29-30 October (2020).
2. C. Mihaescu, C.L. Nistor, C. Petcu, R. Ianchis, C.M. Ninciuleanu, E. Alexandrescu, C. Scomoroscenco, L.O. Cinteza, "Synthesis and Morphological Investigation of Flower-Like ZnO Nanostructures", Priorities of Chemistry for a Sustainable Development - PRIOCHEM XVI ed., Bucharest, Romania, 28-30 October (2020).
3. C. Mihaescu, C.L. Nistor, C. Petcu, R. Ianchis, C.M. Ninciuleanu, E. Alexandrescu, C. Scomoroscenco, L.O. Cinteza, "Silica Nanoparticles Loaded with Curcumin - Encapsulation Efficiency", Priorities of Chemistry for a Sustainable Development - PRIOCHEM XVI ed., Bucharest, Romania, 28-30 October (2020).

1. M.A. Tanase, A. Raducan, P. Oancea, L.M. Ditu , M. Stan, C. Petcu, C. Scomoroscenco, C.M. Ninciuleanu, C.L. Nistor, L.O. Cinteza, "Mixed Pluronic-Cremophor Polymeric Micelles as Nanocarriers for Poorly Soluble Antibiotics - The Influence on the Antibacterial Activity", Pharmaceutics, 2021, 13, 435, (https://doi.org/10.3390/pharmaceutics13040435).
2. C. Scomoroscenco, M. Teodorescu, A. Raducan, M. Stan, S.N. Voicu, B. Trica, C.M. Ninciuleanu, C.L. Nistor, C.I. Mihaescu, C. Petcu, L.O. Cinteza, "Novel gel microemulsion for transdermal delivery of Curcumin in dermatocosmetics", Pharmaceutics, 2021, 13, 505, (https://doi.org/10.3390/pharmaceutics13040505).

1. C. Mihaescu, L.O. Cinteza, C.L. Nistor, C. Petcu, S.G. Burlacu, B. Trica, C. Scomoroscenco, R. Ianchis, C.M. Ninciuleanu, C. Gifu, E. Alexandrescu, "Preliminary Studies on Silica Nanoparticles Preparation as Transport Vectors for Curcumin", Priorities of Chemistry for a Sustainable Development - PRIOCHEM XVII ed., Bucharest, Romania, 27-29 October (2021).
2. C.I. Mihaescu, L.O. Cinteza, C.L. Nistor, C. Petcu, S.G. Burlacu, B. Trica, C. Scomoroscenco, R. Ianchis, C. Ninciuleanu, C. Gifu, E. Alexandrescu, "Synthesis of Silica Particles Loaded with Curcumin and Coated with PEG750", Progress in Organic and Macromolecular Compounds Conference - MACROIASI'2021, Iasi, Romania, 7-9 October (2021).
3. C.I. Mihaescu, C.L. Nistor, L.O. Cinteza, C. Ninciuleanu, E. Alexandrescu, S.G. Burlacu, C. Scomoroscenco, R. Ianchis, B. Trica, C. Gifu, C. Petcu, "Tailored Silica Nanocarriers for Curcumin Delivery", 4th International Conference on Emerging Technologies in Materials Engineering-EmergeMAT, Bucharest, Romania, 4-5 November (2021).
4. C. Scomoroscenco, M. Teodorescu, S.G. Burlacu, I.C. Gifu, C.I. Mihaescu, C. Petcu, C.M. Ninciuleanu, R. Ianchis, C.L. Nistor, L.O. Cinteza, "Mathematical Models Applied to Release Profile and Permeation Study of Curcumin Encapsulated in Microemulsion", 4th International Conference on Emerging Technologies in Materials Engineering-EmergeMAT, Bucharest, Romania, 4-5 November (2021).
5. M.A. Tanase, A.C. Soare, B. Radu, C.L. Nistor, B. Trica, C. Petcu, L.O. Cinteza, "Synthesis, Characterization and Biocompatibility of Anisotropic Silver Nanoparticles", Priorities of Chemistry for a Sustainable Development - PRIOCHEM XVII ed., Bucharest, Romania, 27-29 October (2021).

1. C. Scomoroscenco, M. Teodorescu, S.G. Burlacu, I.C. Gifu, C.I. Mihaescu, C. Petcu, A. Raducan, P. Oancea, L.O. Cinteza, "Synergistic Antioxidant Activity and Enhanced Stability of Curcumin Encapsulated in Vegetal Oil-Based Microemulsion and Gel Microemulsions", Antioxidants, 2022, 11, 854, (https://doi.org/10.3390/antiox11050854).

1. Nistor C.L., Mihaescu C.I., Burlacu S.G., Tanase M.A., Radu B., Cinteza L.O., Petcu C., Ninciuleanu C., Trica B., "Dioctyl Sodium Sulfosuccinate - Templated PEG-Silica Nanoparticles Loaded with Curcumin and Ag NPs", 12^th International Conference on Materials Science & Engineering - BRAMAT 2022, Brasov, Romania, 9-12 March (2022).

1. Trends in the development of nanostructured materials to prevent the formation of β-amyloid fibrils in Alzeheimer's disease, June 21, 2022., 21 June 2022.

1. Technology for obtaining a nanoformulated product, designed for the prevention of Alzheimer's disease, with properties to reduce oxidative stress and to inhibit the formation of β-amyloid plaques.

1. Cristina Lavinia Nistor, Otilia Ludmila Cinteza, Catalin Ionut Mihaescu, Sabina Georgiana Burlacu, Cristian Petcu, Claudia Mihaela Ninciuleanu, Cristina Scomoroscenco, Raluca Ianchis; Ioana Catalina Gifu, "Procees for preparation of an advanced product based on nanoparticles with synergistic effect on neuronal oxidative stress and β-amyloid fibrillation for preventive treatment in Alzheimer's disease", a2022-00126/16.03.2022.

2020

2021

2022