Satyanarayana Somavarapu
UCL School of Pharmacy, UK
Title: Therapeutic potential against metastatic melanoma of a copper-based aquaporin inhibitor nanoformulated
Biography
Biography: Satyanarayana Somavarapu
Abstract
Fisetin or 3, 3’, 4’, 7-tetrahydroxyflavone is a natural flavonoid which can be found in different fruits and vegetables. Apart from its antioxidant, anti-inflammatory and neuroprotective activities, several studies have shown its anticancer effect in several cancer cell lines (e.g. lung, colon and prostate). This study explores the incorporation of fisetin into the cavity of different cyclodextrins to improve its poor aqueous solubility (< 1 mg/ml), that hinders its delivery. The complex was further engineered into an inhalable dry powder formulation that will potentially be useful to target the lung for therapeutic applications.
The highest complexation was found between fisetin and sulfobutylether-β-cyclodextrin (SBE-β-CD), and addition of 20%v/v ethanol increased the complexation by 5.9-fold. The spray-dried complex from the ethanolic solution showed an improved aerosolization performance, indicated by 2-fold increase in the fine particle fraction, compared to the spray-dried complex from aqueous solution. This may be caused by the lighter and less dense properties of the particles, showed by the pitted morphological surfaces, suggesting a hollower internal structure. Further incorporation of 20%w/w leucine improved the physical and aerosolization properties of the spray-dried complex. The preparation also showed an unchanged cytotoxic activity of fisetin against the human lung adenocarcinoma cell line (A549). In conclusion, the inhalable dry powder of fisetin-SBE-β-CD complex was able to increase aqueous solubility of fisetin and may be useful to deliver fisetin to the deep lung region.