Dual-drug loaded nanoparticles of Epigallocatechin-3-gallate (EGCG)/Ascorbic acid enhance therapeutic efficacy of EGCG in a APPswe/PS1dE9 Alzheimer's disease mice model
Open accessAbstract
Epigallocatechin-3-gallate (EGCG) is a candidate for treatment of Alzheimer's disease (AD) but its inherent instability limits bioavailability and effectiveness. We found that EGCG displayed increased stability when formulated as dual-drug loaded PEGylated PLGA nanoparticles (EGCG/AA NPs). Oral administration of EGCG/AA NPs in mice resulted in EGCG accumulation in all major organs, including the brain. Pharmacokinetic comparison of plasma and brain accumulation following oral administration of free or EGCG/AA NPs showed that, whilst in both cases initial EGCG concentrations were similar, long-term (5–25 h) concentrations were ca. 5 fold higher with EGCG/AA NPs. No evidence was found that EGCG/AA NPs utilised a specific pathway across the blood-brain barrier (BBB). However, EGCG, empty NPs and EGCG/AA NPs all induced tight junction disruption and opened the BBB in vitro and ex vivo. Oral treatment of APPswe/PS1dE9 (APP/PS1) mice, a familial model of AD, with EGCG/AA NPs resulted in a marked increase in synapses, as judged by synaptophysin (SYP) expression, and reduction of neuroinflammation as well as amyloid β (Aβ) plaque burden and cortical levels of soluble and insoluble Aβ(1-42) peptide. These morphological changes were accompanied by significantly enhanced spatial learning and memory. Mechanistically, we propose that stabilisation of EGCG in NPs complexes and a destabilized BBB led to higher therapeutic EGCG concentrations in the brain. Thus EGCG/AA NPs have the potential to be developed as a safe and strategy for the treatment of AD.
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Oral delivery of EGCG NP formulation in APP/PS1 AD mouse model reduced neuroinflammation and Aβ plaque.
“In an interesting in vivo study, oral delivery of epigallocatechin-3-gallate (EGCG) NP formulation in an APP/PS1 AD mouse model reduced neuroinflammation and AB plaque (Fig. 3a–c).”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [114]
EGCG in combination with PEGylated PLGA NPs displayed increased stability and sustained release with high bioavailability compared to free EGCG.
“EGCG in combination with PEGylated PLGA NPs (EGCG/AA NPs) displayed increased stability and sustained release with high bioavailability compared to that of free EGCG.”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [114]
EGCG/AA NPs significantly improved spatial learning and memory in APP/PS1 AD mouse model.
“Furthermore, these data were supported by significantly improved spatial learning and memory (Fig. 3d, e).114”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [114]
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Adeola, H. A., Bano, A., Vats, R., Vashishtha, A., Verma, D., Kaushik, D. K., Mittal, V., Rahman, M. H., Najda, A., Albadrani, G. M., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111809 · Cited by 32 · see citing works
RetractedFurniturewalla, A., & Barve, K. H. (2022) · Food Chemistry Advances · doi:10.1016/j.focha.2022.100037 · Cited by 32 · see citing works
- Authors
- Cano, A., Ettcheto, M., Chang, J.-H., Barroso, E., Espina, M., Kühne, B. A., Barenys, M., Auladell, C., Folch, J., Souto, E. B., Camins, A., Turowski, P., & García, M. L.
- Affiliations
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- University College London (GB)
- Hospital Sant Joan de Déu Barcelona (ES)
- Institut de Nanociència i Nanotecnologia de la Universitat de Barcelona (ES)
- Universitat de Barcelona (ES)
- University of Coimbra (PT)
- Corresponding author
- Turowski, Patric
- García, Maria Luisa
- ORCID
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 301
- Pages
- 62-75
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC6510952
- OpenAlex
- W2920901214
- Cited by
- 337
- References
- 87
- Citations by year
- 2026: 31 · 2025: 55 · 2024: 45 · 2023: 52 · 2022: 58 · 2021: 49 · 2020: 38 · 2019: 8
- FWCI
- 26.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Controlled Release (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by-nc-nd)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- British Heart Foundation (FS/16/26/32193)
- Ministerio de Ciencia e Innovación (PI2016/01, SAF2017-84283-R, MAT 2014-59134-R, CB06/05/0024)
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- European Regional Development Fund
- Generalitat de Catalunya (CVE-DOGC-B-14206020-2014)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pathology and Forensic Medicine › Tea Polyphenols and Effects
- Keywords
- epigallocatechin gallate, vitamin C, Alzheimer's disease, APP/PS1 mice, blood-brain barrier disruption, tight junctions, oral bioavailability, brain accumulation, amyloid-beta, neuroinflammation, synaptophysin, spatial learning and memory, drug stability
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Alzheimer Disease, Animals, Antioxidants, Ascorbic Acid, Brain, Catechin, Disease Models, Animal, Drug Carriers, Male, Mice, Inbred C57BL, Mice, Transgenic, Polyethylene Glycols, Amyloid beta-Peptides, Endothelial Cells, Rats, Nanoparticles, Drug Liberation
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