Formulation and optimization of silymarin-encapsulated binary micelles for enhanced amyloid disaggregation activity
Silymarin (SLY) is a natural hydrophobic polyphenol that possesses antioxidant and amyloid fibril (Aβ1-42) inhibition activity, but its activity is hindered due to low aqueous solubility. In this study, SLY is encapsulated in binary micelle (SLY-BM) that has been utilized to enhance the Aβ1-42 fibril disaggregation. To enhance the aqueous solubility, SLY payload in micelles were optimized using Box-Behnken Design (BBD) to increase the efficiency of Aβ1-42 fibril disaggregation. BBD was used to investigate the effect of ratio of Solutol HS15:Poloxamer-188, amount of acetone and hydration volume on critical quality attributes, particle size, and entrapment efficiency for SLY-BM. Furthermore, SLY-BM was characterized for its physical and drug release properties. The Aβ1-42 fibril disaggregation and antioxidant studies were monitored using spectroscopic and microscopic techniques. BBD optimized the particle size <50 nm with %EE > 80%, and solubility factor of SLY-BM was enhanced to 460 folds than free SLY. Inhibitory concentration 50% (IC50) value of SLY-BM was 19.67 µg/mL compared to free SLY (30.06 µg/mL) in diphenylpicrahydrazyl assay. SLY-BM increased the Aβ1-42 disaggregation compared to free SLY observed via thioflavin-T assay, photon correlation spectroscopy, and circular dichorism. Further morphological evaluation of Aβ1-42 disaggregation was monitored by microscopy which showed that SLY-BM disaggregated the fibrils in 48 h. According to our findings, we concluded that SLY-BM micelles are potential candidates for delivery of neuroprotective agents.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:47 |
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| Enthalten in: |
Drug development and industrial pharmacy - 47(2021), 11 vom: 28. Nov., Seite 1775-1785 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Singh, Ajit [VerfasserIn] |
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| Links: |
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| Themen: |
Aβ1–42 disaggregation |
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| Anmerkungen: |
Date Completed 23.06.2022 Date Revised 23.06.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/03639045.2022.2059498 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM338735348 |
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| 520 | |a Silymarin (SLY) is a natural hydrophobic polyphenol that possesses antioxidant and amyloid fibril (Aβ1-42) inhibition activity, but its activity is hindered due to low aqueous solubility. In this study, SLY is encapsulated in binary micelle (SLY-BM) that has been utilized to enhance the Aβ1-42 fibril disaggregation. To enhance the aqueous solubility, SLY payload in micelles were optimized using Box-Behnken Design (BBD) to increase the efficiency of Aβ1-42 fibril disaggregation. BBD was used to investigate the effect of ratio of Solutol HS15:Poloxamer-188, amount of acetone and hydration volume on critical quality attributes, particle size, and entrapment efficiency for SLY-BM. Furthermore, SLY-BM was characterized for its physical and drug release properties. The Aβ1-42 fibril disaggregation and antioxidant studies were monitored using spectroscopic and microscopic techniques. BBD optimized the particle size <50 nm with %EE > 80%, and solubility factor of SLY-BM was enhanced to 460 folds than free SLY. Inhibitory concentration 50% (IC50) value of SLY-BM was 19.67 µg/mL compared to free SLY (30.06 µg/mL) in diphenylpicrahydrazyl assay. SLY-BM increased the Aβ1-42 disaggregation compared to free SLY observed via thioflavin-T assay, photon correlation spectroscopy, and circular dichorism. Further morphological evaluation of Aβ1-42 disaggregation was monitored by microscopy which showed that SLY-BM disaggregated the fibrils in 48 h. According to our findings, we concluded that SLY-BM micelles are potential candidates for delivery of neuroprotective agents | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Verma, Rahul K |e verfasserin |4 aut | |
| 700 | 1 | |a Shukla, Rahul |e verfasserin |4 aut | |
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