Formulation of Rutin Lipid Nanoparticles‐Based Gel: in vitro Characterization, Molecular Docking and Cytotoxicity Assessment

Abstract Rutin (RT) is a water‐insoluble flavonoid reported for different biological activities including anticancer activity. Its activity is limited due to the poor aqueous solubility. To overcome drawbacks, nano‐sized amphiphilic lipid particles (RTLNPs) were developed using glyceryl monostearate (solid lipid), poloxamer 188 as well as tween 80 (surfactant). The different ratios were used to prepare and optimize RTLNPs by melt emulsification followed by the ultrasonication method. The developed RTLNPs were evaluated for particle size (PS), surface charge (ZP), encapsulation efficiency (EE), drug‐polymer interaction (IR, DSC, XRD), and in vitro drug release. The optimized RTLNPs (RT2) were further converted to transdermal gel using a polymer blend (Carbopol and HPMC). Further, the prepared gels (RTLNPsG) were evaluated for gel characterization, membrane permeation (Strat‐M membrane), antioxidant, cytotoxicity (skin cancer), and molecular docking study. RTLNPs were successfully prepared using the method and depicted in nanometric size range, low PDI, negative surface charge, and high encapsulation efficiency. It has shown the maximum drug release of 71.2 ± 2.1% in 24 h with biphasic release behavior. There was no RT polymer interaction observed confirmed by the IR study. DSC and XRD result in the conversion of crystalline RT into an amorphous form. The gel characterization revealed optimum gel properties and enhanced permeation compared to the control RT gel. It also displayed better in vitro antioxidants and exhibited better cytotoxicity activity against skin cancer cells than pure RT. The binding energy score (−5.52 Kcal/mol) supports the finding of the cell viability assay.