Silymarin loaded nanostructured lipid carrier: From design and dermatokinetic study to mechanistic analysis of epidermal drug deposition enhancement

Abstract

This investigation aimed to develop nanostructured lipid carrier (NLC) gel of silymarin for epidermal tissue deposition enhancement. Binary mixture of solid lipid and liquid lipid was optimized in term of crystallinity, enthalpy of fusion and width of thermal event using DSC. NLC formulation was optimized using central composite rotatable design (CCRD). Optimized freeze dried NLC dispersion containing Sefsol® 218 (0.5% w/w), Geleol® (1.4% w/w), bile salt (1.3% w/w), Cremophor® RH40 (2.7% w/w) and mannitol (3.0% w/w) was characterized for mean particle size (PS), polydispersability index (PDI), zeta potential (ZP) and entrapment efficiency (EE). PS, PDI, ZP and EE were found to be 126.1±0.4nm, 0.33±0.03, −28.8±0.7mV and 85.0±2.9%, respectively. In vitro (Strat-M™ membrane) and ex vivo (rat skin) permeation studies showed close correlation (r2=0.98). The flux and permeability coefficient of NLC gel in ex vivo permeation studies were found to be 23.6μg/cm2/h and 23.6×10−3cm/h respectively. Dermatokinetic study showed a significant (p<0.001) increase in CSkin max and AUC0–8h in skin treated with NLC gel as compared to skin treated with conventional gel. Confocal microscopic (CLMS) studies depicted maximum silymarin deposition in viable epidermis (30μm). FTIR and DSC analysis indicated lipid bilayer fluidization mechanism of epidermal drug deposition enhancement. Skin irritation studies confirmed the nonirritant behavior of NLC gel to skin. These findings show that NLC gel can be used as a potential carrier for topical delivery of silymarin.