Inhibition of Aβ Aggregation by Cholesterol-End-Modified PEG Vesicles and Micelles
<b>Background/Objectives</b>: This study aimed to design and evaluate Chol-PEG<sub>2000</sub> micelles and Chol-PEG<sub>500</sub> vesicles as drug delivery system (DDS) carriers and inhibitors of amyloid-β (Aβ) aggregation, a key factor in Alzheimer’s disease (AD)...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/17/1/1 |
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| Summary: | <b>Background/Objectives</b>: This study aimed to design and evaluate Chol-PEG<sub>2000</sub> micelles and Chol-PEG<sub>500</sub> vesicles as drug delivery system (DDS) carriers and inhibitors of amyloid-β (Aβ) aggregation, a key factor in Alzheimer’s disease (AD). <b>Methods</b>: The physical properties of Chol-PEG assemblies were characterized using dynamic light scattering (DLS), electrophoretic light scattering (ELS), and transmission electron microscopy (TEM). Inhibitory effects on Aβ aggregation were assessed via thioflavin T (ThT) assay, circular dichroism (CD) spectroscopy, and native polyacrylamide gel electrophoresis (native-PAGE). <b>Results</b>: Chol-PEG<sub>2000</sub> micelles and Chol-PEG<sub>500</sub> vesicles were found to exhibit diameters of 20–30 nm and 70–80 nm, respectively, with neutral surface charges and those physical properties indicated the high affinity for Aβ. At a 10-fold molar ratio, thioflavin T (ThT) assay revealed that Chol-PEG<sub>2000</sub> delayed Aβ fibril elongation by 20 hours, while Chol-PEG<sub>500</sub> delayed it by 40 hours against Aβ peptide. At a 50-fold molar ratio, both Chol-PEG<sub>2000</sub> and Chol-PEG<sub>500</sub> significantly inhibited Aβ aggregation, as indicated by minimal fluorescence intensity increases over 48 hours. CD spectroscopy indicated that Aβ maintained its random coil structure in the presence of Chol-PEG assemblies at a 50-fold molar ratio. Native-PAGE analysis demonstrated a retardation in Aβ migration immediately after mixing with Chol-PEG assemblies, suggesting complex formation. However, this retardation disappeared within 5 min, implying rapid dissociation of the complexes. <b>Conclusions</b>: This study demonstrated that Chol-PEG<sub>500</sub> vesicles more effectively inhibit Aβ aggregation than Chol-PEG<sub>2000</sub> micelles. Chol-PEG assemblies perform as DDS carriers to be capable of inhibiting Aβ aggregation. Chol-PEG assemblies can deliver additional therapeutics targeting other aspects of AD pathology. This dual-function platform shows promise as both a DDS carrier and a therapeutic agent, potentially contributing to a fundamental cure for AD. |
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| ISSN: | 1999-4923 |