Enhanced Chemical Stability of Hirsutenone Incorporated into a Nanostructured Lipid Carrier Formulation Containing Antioxidants

摘要

To enhance the chemical stability of hirsutenone (HST), a natural diarylheptanoid, nanostructured lipid carrier (NLC) formulations containing antioxidants were employed. The stability and shelf-life of HST-containing formulations were assessed by using accelerated aging tests. Drug-free NLC formulations, using Compritol 888 ATO as a solid lipid, Labrafil M1944 CS as an oil, and Tween 80 as a surfactant, had a particle size of approximately 177 nm, a polydispersity index of 0.257, and a zeta potential of -15.5 mV. Drag- or antioxidant-loading slightly increased the particle size but did not alter the surface charge of the NLC formulations. HST entrapment efficiencies were 86.83% and 88.19% for antioxidant-free and antioxidant-added NLC formulations, respectively. NLC formulations extended the half-life of HST relative to aqueous solutions, but the stabilizing effect was unsatisfactory. The use of 1% ascorbyl palmitate (AP) and 1% ethylenediaminetetraacetic acid (EDTA) in the NLC formulations resulted in the greatest stabilization of HST, with a half-life of approximately 120 days at 40°C. The stability assessments of different NLC formulations were conducted based on the first-order kinetics and the shelf-life at different temperatures was estimated by using the Q_(10) method. Assuming a Q_(10) value of 2, the shelf-life of AP/EDTA-added NLC formulations at 25°C and 4 °C was 51.2 and 219.5 days, respectively. Although the HST stability was considerably enhanced by NLC formulation and further improved by adding antioxidants, alternative studies to assure the sufficient stability and enable the practical application of NLC formulations in product development are still required.