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Liposomes Decorated with 2-(4'-Aminophenyl)benzothiazole Effectively Inhibit Aβ 1-42 Fibril Formation and Exhibit in Vitro Brain-Targeting Potential.
- Source :
-
Biomacromolecules [Biomacromolecules] 2020 Dec 14; Vol. 21 (12), pp. 4685-4698. Date of Electronic Publication: 2020 Oct 28. - Publication Year :
- 2020
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Abstract
- The potential of 2-benzothiazolyl-decorated liposomes as theragnostic systems for Alzheimer's disease was evaluated in vitro, using PEGylated liposomes that were decorated with two types of 2-benzothiazoles: (i) the unsubstituted 2-benzothiazole (BTH) and (ii) the 2-(4-aminophenyl)benzothiazole (AP-BTH). The lipid derivatives of both BTH-lipid and AP-BTH-lipid were synthesized, for insertion in liposome membranes. Liposomes (LIP) containing three different concentrations of benzothiazoles (5, 10, and 20%) were formulated, and their stability, integrity in the presence of serum proteins, and their ability to inhibit β-amyloid (1-42) (Αβ42) peptide aggregation (by circular dichroism (CD) and thioflavin T (ThT) assay), were evaluated. Additionally, the interaction of some LIP with an in vitro model of the blood-brain barrier (BBB) was studied. All liposome types ranged between 92 and 105 nm, with the exception of the 20% AP-BTH-LIP that were larger (180 nm). The 5 and 10% AP-BTH-LIP were stable when stored at 4 °C for 40 days and demonstrated high integrity in the presence of serum proteins for 7 days at 37 °C. Interestingly, CD experiments revealed that the AP-BTH-LIP substantially interacted with Αβ42 peptides and inhibited fibril formation, as verified by ThT assay, in contrast with the BTH-LIP, which had no effect. The 5 and 10% AP-BTH-LIP were the most effective in inhibiting Αβ42 fibril formation. Surprisingly, the AP-BTH-LIP, especially the 5% ones, demonstrated high interaction with brain endothelial cells and high capability to be transported across the BBB model. Taken together, the current results reveal that the 5% AP-BTH-LIP are of high interest as novel targeted theragnostic systems against AD, justifying further in vitro and in vivo exploitation.
Details
- Language :
- English
- ISSN :
- 1526-4602
- Volume :
- 21
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Biomacromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 33112137
- Full Text :
- https://doi.org/10.1021/acs.biomac.0c00811