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Título: | Brain-Targeted Delivery of Pre-miR-29b Using Lactoferrin-Stearic Acid-Modified-Chitosan/Polyethyleneimine Polyplexes | Autor: | Pereira, Patrícia Barreira, Maria Cruz, Carla Tomás, Joana Luís, Ângelo Pedro, Augusto Q. Queiroz, João A. Sousa, Fani |
Palavras-chave: | blood–brain barrier; chitosan; drug delivery system; lactoferrin; polyethyleneimine; recombinant miRNA | Data: | 15-Out-2020 | Editora: | MDPI | Projeto: | Pest-OE/SAU/UI0709/2014 UIDB/50011/2020 UIDP/50011/2020 UIDB/50011/2020 UIDP/50011/2020 info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC/BII-BBF/29496/2017/PT/Ionic Liquid-based supports for pre-miRNAs purification targeting Alzheimer's disease info:eu-repo/grantAgreement/FCT/9444 - RNIIIE/PINFRA/22161/2016/PT/Portuguese Nuclear Magnetic Resonance Network |
Título da revista, periódico, livro ou evento: | Pharmaceuticals | Volume: | 13 | Número: | 10 | Resumo: | 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. | URI: | https://hdl.handle.net/10316/106532 | ISSN: | 1424-8247 | DOI: | 10.3390/ph13100314 | Direitos: | openAccess |
Aparece nas coleções: | I&D CEMMPRE - Artigos em Revistas Internacionais FCTUC Eng.Química - Artigos em Revistas Internacionais |
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Ficheiro | Descrição | Tamanho | Formato | |
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Braintargeted-delivery-of-premir29b-using-lactoferrinstearic-acidmodifiedchitosan-polyethyleneimine-polyplexesPharmaceuticals.pdf | 3.52 MB | Adobe PDF | Ver/Abrir |
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