Memantine loaded PLGA PEGylated nanoparticles for Alzheimer¿s disease: in vitro and in vivo characterization

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Sánchez-López, E (Author) Other; Ettcheto, M (Author) Other; Egea, MA (Author) Other; Espina, M (Author) Other; Cano, A (Author) Other; Calpena, AC (Author) Other; Camins, A (Author) Other; Carmona, N (Author) Other; Silva, AM (Author) Other; Souto, EB (Author) Other; García, ML (Author) Other

Journal

Title: Journal of Nanobiotechnology

Vol. 25

ISSN: 1477-3155

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 9 Citations

Scopus - 57 Citations

Other information

Authenticus ID: P-00Y-1FS

DOI: 10.1186/s12951-018-0356-z

Abstract (EN): Background: Memantine, drug approved for moderate to severe Alzheimer's disease, has not shown to be fully effective. In order to solve this issue, polylactic-co-glycolic (PLGA) nanoparticles could be a suitable solution to increase drug's action on the target site as well as decrease adverse effects. For these reason, Memantine was loaded in biodegradable PLGA nanoparticles, produced by double emulsion method and surface-coated with polyethylene glycol. MEM-PEG-PLGA nanoparticles (NPs) were aimed to target the blood-brain barrier (BBB) upon oral administration for the treatment of Alzheimer's disease. Results: The production parameters were optimized by design of experiments. MEM-PEG-PLGA NPs showed a mean particle size below 200 nm (152.6 +/- 0.5 nm), monomodal size distribution (polydispersity index, PI < 0.1) and negative surface charge (-22.4 mV). Physicochemical characterization of NPs confirmed that the crystalline drug was dispersed inside the PLGA matrix. MEM-PEG-PLGA NPs were found to be non-cytotoxic on brain cell lines (bEnd.3 and astrocytes). Memantine followed a slower release profile from the NPs against the free drug solution, allowing to reduce drug administration frequency in vivo. Nanoparticles were able to cross BBB both in vitro and in vivo. Behavioral tests carried out on transgenic APPswe/PS1dE9 mice demonstrated to enhance the benefit of decreasing memory impairment when using MEM-PEG-PLGA NPs in comparison to the free drug solution. Histological studies confirmed that MEM-PEG-PLGA NPs reduced beta-amyloid plaques and the associated inflammation characteristic of Alzheimer's disease. Conclusions: Memantine NPs were suitable for Alzheimer's disease and more effective than the free drug.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 16