Formulation and optimization of silymarin-encapsulated binary micelles for enhanced amyloid disaggregation activity

• Published in: Drug development and industrial pharmacy Vol. 47; no. 11; pp. 1775 - 1785
• Main Authors: Singh, Ajit, Ujjwal, Rewati Raman, Kumar, Ashish, Verma, Rahul K., Shukla, Rahul
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.11.2021
• Subjects: 1-42; Antioxidant; binary micelle; Box-Behnken design; disaggregation; Silymarin; binary micelle; Box–Behnken design; Silymarin; Antioxidant; Aβ1–42 disaggregation
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1080/03639045.2022.2059498

Silymarin (SLY) is a natural hydrophobic polyphenol that possesses antioxidant and amyloid fibril (Aβ 1-42 ) 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 Aβ 1-42 fibril disaggregation. To enhance the aqueous solubility, SLY payload in micelles were optimized using Box-Behnken Design (BBD) to increase the efficiency of Aβ 1-42 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 Aβ 1-42 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% (IC 50 ) value of SLY-BM was 19.67 µg/mL compared to free SLY (30.06 µg/mL) in diphenylpicrahydrazyl assay. SLY-BM increased the Aβ 1-42 disaggregation compared to free SLY observed via thioflavin-T assay, photon correlation spectroscopy, and circular dichorism. Further morphological evaluation of Aβ 1-42 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.