Loading of hydrophobic drug silymarin in pluronic and reverse pluronic mixed micelles

Abstract

In the presented work, pure pluronic and mixed micelles of normal pluronics (F108, F127, P85 and P84) with reverse pluronic (10R5) have been studied to enhance the solubilization of the hydrophobic drug silymarin (SLY) at different % w/v proportions (4:1, 2.5, 1:4 and 5). Solubilization capacity of SLY in the mixed micelles was found to be higher than pure pluronic micelles. Drug solubilization parameters including drug loading efficiency (DL), partition coefficient (P) and Gibbs free energy of solubilization (ΔG◦) were calculated. SLY loaded mixed micellar formulation of P84:10R5 (4:1% w/v) showed maximum solubility and drug loading efficiency as compared to other mixed micellar formulations. The cmc of pure as well as mixed micellar systems has been evaluated using fluorescence measurements. The locus of SLY in these micelles was evaluated by micropolarity measurements. After solubilization, increase in hydrodynamic size evidenced by DLS measurements confirmed the solubilization of SLY in the mixed micelles. In vitro drug release study was also performed for mixed micellar formulations with maximum SLY solubilization, and it was found to exhibit sustained release drug behavior. Different kinetics models were also applied and the best fitted model for the optimum SLY loaded mixed micellar formulation was found to be the Korsmeyer-Peppas model. To investigate the anti-oxidative potential of SLY drug and SLY loaded mixed micellar formulation of P84:10R5 (4:1% w/v),1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH·) scavenging, ferrous ions (Fe2+) chelating activities, total reducing ability determination by Fe3+ to Fe2+ transformation method, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging and nitric oxide assay were undertaken. The SLY loaded mixed micellar formulation of P84:10R5 (4:1% w/v) exhibited appreciably enhanced anti-oxidative activity as compared to SLY alone.