Tailoring Lipid and Polymeric Nanoparticles as siRNA Carriers towards the Blood-Brain Barrier - from Targeting to Safe Administration

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Gomes, MJ (Author) Other; Fernandes, C (Author) Other; Martins, S (Author) Other; Fernanda Borges (Author) FCUP; Sarmento, B (Author) Other

Journal

Title: Journal of NeuroImmune Pharmacology

Vol. 12

Pages: 107-119

ISSN: 1557-1890

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 38 Citations

Scopus - 41 Citations

Other information

Authenticus ID: P-00K-GN7

DOI: 10.1007/s11481-016-9685-6

Abstract (EN): Blood-brain barrier is a tightly packed layer of endothelial cells surrounding the brain that acts as the main obstacle for drugs enter the central nervous system (CNS), due to its unique features, as tight junctions and drug efflux systems. Therefore, since the incidence of CNS disorders is increasing worldwide, medical therapeutics need to be improved. Consequently, aiming to surpass blood-brain barrier and overcome CNS disabilities, silencing P-glycoprotein as a drug efflux transporter at brain endothelial cells through siRNA is considered a promising approach. For siRNA enzymatic protection and efficient delivery to its target, two different nanoparticles platforms, solid lipid (SLN) and poly-lactic-co-glycolic (PLGA) nanoparticles were used in this study. Polymeric PLGA nanoparticles were around 115 nm in size and had 50 % of siRNA association efficiency, while SLN presented 150 nm and association efficiency close to 52 %. Their surface was functionalized with a peptide-binding transferrin receptor, in a site-oriented manner confirmed by NMR, and their targeting ability against human brain endothelial cells was successfully demonstrated by fluorescence microscopy and flow cytometry. The interaction of modified nanoparticles with brain endothelial cells increased 3-fold compared to non-modified lipid nanoparticles, and 4-fold compared to non-modified PLGA nanoparticles, respectively. These nanosystems, which were also demonstrated to be safe for human brain endothelial cells, without significant cytotoxicity, bring a new hopeful breath to the future of brain diseases therapies.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13