PMID- 36075524 OWN - NLM STAT- MEDLINE DCOM- 20220929 LR - 20220929 IS - 1873-3476 (Electronic) IS - 0378-5173 (Linking) VI - 626 DP - 2022 Oct 15 TI - Transferrin-functionalized liposomes loaded with vitamin VB12 for Alzheimer's disease therapy. PG - 122167 LID - S0378-5173(22)00721-9 [pii] LID - 10.1016/j.ijpharm.2022.122167 [doi] AB - Despite the efforts of the pharmaceutical and research sectors, Alzheimer's disease (AD) remains incurable, imposing the demand for new effective strategies. Vitamin B12 (VB12) has aroused interest due to its in vitro anti-amyloidogenic properties. However, the high molecular weight and hydrophilicity of VB12 are the main obstacles to its clinical application by hindering its passage through the blood-brain barrier (BBB). In recent years, drug delivery systems (DDSs) capable of transporting molecules across the BBB have gained attention for their effective brain delivery. In this work, VB12-loaded liposomes functionalized with transferrin (Tf) were produced, envisaging the dual-targeting of VB12 to the BBB and neuronal cells, due to the overexpression of Tf receptors in these cells. The produced liposomes presented sizes smaller than 200 nm, with low polydispersity and neutral zeta potential, being suitable for brain delivery. The nanoparticles exhibited an adequate encapsulation efficiency, a sustained release of VB12 for 9 days, and physical stability at storage conditions for up to 2 months. The developed nanosystem was capable of delaying the formation of Abeta fibrils and disrupting mature fibrils, highlighting its great potential for the prevention and treatment of AD. CI - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Andrade, Stephanie AU - Andrade S AD - LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal. FAU - Ramalho, Maria J AU - Ramalho MJ AD - LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal. FAU - Loureiro, Joana A AU - Loureiro JA AD - LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal. Electronic address: jasl@fe.up.pt. FAU - Pereira, Maria C AU - Pereira MC AD - LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal. Electronic address: mcsp@fe.up.pt. LA - eng PT - Journal Article DEP - 20220906 PL - Netherlands TA - Int J Pharm JT - International journal of pharmaceutics JID - 7804127 RN - 0 (Delayed-Action Preparations) RN - 0 (Liposomes) RN - 0 (Transferrin) RN - 0 (Vitamins) RN - P6YC3EG204 (Vitamin B 12) SB - IM MH - *Alzheimer Disease/drug therapy MH - Blood-Brain Barrier/metabolism MH - Delayed-Action Preparations/pharmacology MH - Humans MH - Liposomes/pharmacology MH - *Nanoparticles MH - Transferrin/metabolism MH - Vitamin B 12 MH - Vitamins OTO - NOTNLM OT - Amyloid beta-peptide OT - Blood-brain barrier OT - Brain targeting OT - Lipid vesicle OT - Nanoparticle OT - Targeted delivery COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/09/09 06:00 MHDA- 2022/09/30 06:00 CRDT- 2022/09/08 19:35 PHST- 2022/04/26 00:00 [received] PHST- 2022/08/11 00:00 [revised] PHST- 2022/08/30 00:00 [accepted] PHST- 2022/09/09 06:00 [pubmed] PHST- 2022/09/30 06:00 [medline] PHST- 2022/09/08 19:35 [entrez] AID - S0378-5173(22)00721-9 [pii] AID - 10.1016/j.ijpharm.2022.122167 [doi] PST - ppublish SO - Int J Pharm. 2022 Oct 15;626:122167. doi: 10.1016/j.ijpharm.2022.122167. Epub 2022 Sep 6.