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Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer's Disease-Related Pathology in APP/PS-1 Mice.
- Source :
-
International journal of nanomedicine [Int J Nanomedicine] 2020 Apr 23; Vol. 15, pp. 2841-2858. Date of Electronic Publication: 2020 Apr 23 (Print Publication: 2020). - Publication Year :
- 2020
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Abstract
- Introduction: Osthole (Ost) is a coumarin compound that strengthens hippocampal neurons and neural stem cells against Aβ oligomer-induced neurotoxicity in mice, and is a potential drug for the treatment of Alzheimer's disease (AD). However, the effectiveness of the drug is limited by its solubility and bioavailability, as well as by the low permeability of the blood-brain barrier (BBB). In this study, a kind of transferrin-modified Ost liposomes (Tf-Ost-Lip) was constructed, which could improve the bioavailability and enhance brain targeting.<br />Methods: Tf-Ost-Lip was prepared by thin-film hydration method. The ability of liposomal formulations to translocate across BBB was investigated using in vitro BBB model. And the protective effect of Tf-Ost-Lip was evaluated in APP-SH-SY5Y cells. In addition, we performed pharmacokinetics study and brain tissue distribution analysis of liposomal formulations in vivo. We also observed the neuroprotective effect of the varying formulations in APP/PS-1 mice.<br />Results: In vitro studies reveal that Tf-Ost-Lip could increase the intracellular uptake of hCMEC/D3 cells and APP-SH-SY5Y cells, and increase the drug concentration across the BBB. Additionally, Tf-Ost-Lip was found to exert a protective effect on APP-SH-SY5Y cells. In vivo studies of pharmacokinetics and the Ost distribution in brain tissue indicate that Tf-Ost-Lip prolonged the cycle time in mice and increased the accumulation of Ost in the brain. Furthermore, Tf-Ost-Lip was also found to enhance the effect of Ost on the alleviation of Alzheimer's disease-related pathology.<br />Conclusion: Transferrin-modified liposomes for delivery of Ost has great potential for AD treatment.<br />Competing Interests: The authors report no conflicts of interest in this work.<br /> (© 2020 Kong et al.)
- Subjects :
- Alzheimer Disease pathology
Animals
Blood-Brain Barrier metabolism
Brain drug effects
Brain pathology
Cell Line
Coumarins chemistry
Coumarins pharmacokinetics
Humans
Liposomes chemistry
Liposomes pharmacokinetics
Mice, Transgenic
Neurons drug effects
Neuroprotective Agents chemistry
Neuroprotective Agents pharmacokinetics
Polyethylene Glycols chemistry
Presenilin-1 genetics
Rats, Sprague-Dawley
Tissue Distribution
Transferrin chemistry
Alzheimer Disease drug therapy
Blood-Brain Barrier drug effects
Coumarins pharmacology
Liposomes pharmacology
Neuroprotective Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1178-2013
- Volume :
- 15
- Database :
- MEDLINE
- Journal :
- International journal of nanomedicine
- Publication Type :
- Academic Journal
- Accession number :
- 32425521
- Full Text :
- https://doi.org/10.2147/IJN.S239608