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Open AccessArticle

Brain-Targeted Delivery of Pre-miR-29b Using Lactoferrin-Stearic Acid-Modified-Chitosan/Polyethyleneimine Polyplexes

1
CICS-UBI-Health Sciences Research Centre, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilhã, Portugal
2
Department of Chemical Engineering, Centre for Mechanical Engineering, Materials and Processes, University of Coimbra, Rua Sílvio Lima-Polo II, 3030-790 Coimbra, Portugal
3
CICECO-Aveiro Institute of Materials, Chemistry Department, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(10), 314; https://doi.org/10.3390/ph13100314
Received: 11 September 2020 / Revised: 3 October 2020 / Accepted: 12 October 2020 / Published: 15 October 2020
(This article belongs to the Special Issue Therapeutic Agents for Neurological Disorders)
The efficacy of brain therapeutics is largely hampered by the presence of the blood–brain barrier (BBB), mainly due to the failure of most (bio) pharmaceuticals to cross it. Accordingly, this study aims to develop nanocarriers for targeted delivery of recombinant precursor microRNA (pre-miR-29b), foreseeing a decrease in the expression of the BACE1 protein, with potential implications in Alzheimer’s disease (AD) treatment. Stearic acid (SA) and lactoferrin (Lf) were successfully exploited as brain-targeting ligands to modify cationic polymers (chitosan (CS) or polyethyleneimine (PEI)), and its BBB penetration behavior was evaluated. The intracellular uptake of the dual-targeting drug delivery systems by neuronal cell models, as well as the gene silencing efficiency of recombinant pre-miR-29b, was analyzed in vitro. Labeled pre-miR-29b-CS/PEI-SA-Lf systems showed very strong fluorescence in the cytoplasm and nucleus of RBE4 cells, being verified the delivery of pre-miR-29b to neuronal cells after 1 h transfection. The experiment of transport across the BBB showed that CS-SA-Lf delivered 65% of recombinant pre-miR-29b in a period of 4 h, a significantly higher transport ratio than the 42% found for PEI-SA-Lf in the same time frame. Overall, a novel procedure for the dual targeting of DDS is disclosed, opening new perspectives in nanomedicines delivery, whereby a novel drug delivery system harvests the merits and properties of the different immobilized ligands. View Full-Text
Keywords: blood–brain barrier; chitosan; drug delivery system; lactoferrin; polyethyleneimine; recombinant miRNA blood–brain barrier; chitosan; drug delivery system; lactoferrin; polyethyleneimine; recombinant miRNA
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MDPI and ACS Style

Pereira, P.; Barreira, M.; Cruz, C.; Tomás, J.; Luís, Â.; Pedro, A.Q.; Queiroz, J.A.; Sousa, F. Brain-Targeted Delivery of Pre-miR-29b Using Lactoferrin-Stearic Acid-Modified-Chitosan/Polyethyleneimine Polyplexes. Pharmaceuticals 2020, 13, 314.

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