Supercritical Fluid Technology-Based Trans-Resveratrol SLN for Long Circulation and Improved Radioprotection

To alleviate the harmful effects of radiations during occupational radiology, radiotherapy and diagnosis, radioprotective system with lower toxicity and extended activity is imperative. Trans-resveratrol (RVL) acts through free radical scavenging/antioxidant mechanism to mitigate the radiation-induced damage. But, its poor solubility and fast metabolism impede its efficacy. Thus, encapsulation of RVL into long circulating solid lipid nanoparticle (SLN) is aimed. Supercritical CO2 solution of RVL, GelucireA (R) 50/02 and GelucireA (R) 50/13 SLN, was rapidly expanded into aqueous phase containing Tween 80, sonicated and lyophilized to get SLN. Particle size, polydispersity index (PDI), entrapment efficiency (%EE), scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), drug release, in vivo pharmacokinetics, antioxidant assays, radiation-induced lipid peroxidation and plasmid DNA relaxation assays were studied. Stability studies were performed to analyze drug degradation and shelf life. Optimized formulation (F9) had %yield, particle size, PDI, %EE and %drug release (after 72 h) of 68.48 +/- 5.73 %, 276.7 +/- 5.33 nm, 0.18 +/- 0.032, 62.66 +/- 4.52 % and 70.05 +/- 3.003 %, respectively. Electron microscopy revealed nearly spherical particles, while DSC and XRD showed reduced crystalline peaks. F9 showed higher AUC and sustained release of RVL in rats (i.v. bolus) and increased antioxidant activities and radioprotection as compared to RVL solution. Shelf life of > 2 years was predicted for F9 (at 8 A degrees C). Results are encouraging to use F9 for radiation exposure prophylaxis.