Brain-Targeted Delivery of Pre-miR-29b Using Lactoferrin-Stearic Acid-Modified-Chitosan/Polyethyleneimine Polyplexes
| Autor: | Joana Tomás, Maria Barreira, João A. Queiroz, Carla Cruz, Augusto Q. Pedro, Patricia N R Pereira, Fani Sousa, Ângelo Luís |
|---|---|
| Přispěvatelé: | uBibliorum |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Drug delivery system Cell lcsh:Medicine lcsh:RS1-441 Pharmaceutical Science Blood–brain barrier blood–brain barrier Article law.invention lcsh:Pharmacy and materia medica Chitosan 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine law recombinant miRNA Drug Discovery medicine Polyethyleneimine drug delivery system Blood-brain barrier biology Lactoferrin lcsh:R Transfection 3. Good health lactoferrin Recombinant miRNA 030104 developmental biology medicine.anatomical_structure chemistry Drug delivery Recombinant DNA biology.protein Biophysics Molecular Medicine Nanocarriers chitosan polyethyleneimine 030217 neurology & neurosurgery |
| Zdroj: | Pharmaceuticals Volume 13 Issue 10 Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) Agência para a Sociedade do Conhecimento (UMIC)-FCT-Sociedade da Informação instacron:RCAAP Pharmaceuticals, Vol 13, Iss 314, p 314 (2020) |
| ISSN: | 1424-8247 |
| DOI: | 10.3390/ph13100314 |
| Popis: | The efficacy of brain therapeutics is largely hampered by the presence of the blood&ndash 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&rsquo 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. |
| Databáze: | OpenAIRE |
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