Optimization of orthosiphon stamineus-loaded nanostructured lipid carrier using d-optimal mixture design for improved lipolysis activity

Abstract

Orthosiphon stamineus (OS) is a Malaysian medicinal herb that was reported to have weight reduction effect and normally prepared as herbal infusion. Effective topical utilization of OS requires a good drug delivery system in order to overcome the stratum corneum to reach the targeted area. Nanostructured lipid carrier (NLC) is a promising carrier for topical drug delivery. The goal of the present study was to optimize the formulation of OS-loaded nanostructured lipid carrier (OS-NLC) for improved lipolysis activity. OS-NLC was prepared using melt emulsification homogenization technique with different types of lipid to obtain good homogeneity and miscibility of the formulation. The result revealed the preferred selection of glyceryl monostearate as solid lipid and triglyceride as liquid lipid since they showed good homogeneity. The formulation of OS-NLC was optimized using D-optimal mixture design which consisted of an amount of active ingredients, solid lipid, and liquid lipid as independent variables while particle size, polydispersity index (PDI) and encapsulation efficiency as dependent variables. From the study, it was found that the optimum formulation of OS-NLC was made of 4% OS, 1% glyceryl monostearate, and 5% triglyceride with 88.57 ± 1.187 nm particle size, 0.135 ± 0.007 PDI and 98.10 ± 1.101 % encapsulation efficiency. Coefficient of determination (R2) indicated a good fit between predicted values and the experimental data points for particle size, PDI and encapsulation efficiency, which were found to be 0.9404, 0.9138 and 0.8754, respectively. Transmission electron microscopy images exhibited the spherical shape of OS-NLC. Fourier transform infrared spectroscopy analysis demonstrated an interaction between OS extract and NLC system. The zeta potential of OS-NLC was -16.7 ± 0.5033 mV. Storage stability of OS-NLC was conducted at cold and room temperature for one month by measuring the particle size, PDI and zeta potential. The results revealed that there were no significant changes in particle size, PDI and zeta potential within one month. The in vitro penetration study using Franz diffusion cell showed that the penetration flux of OS-NLC (2188.74 μg cm-1h-1) was significantly higher than OS (1614.20 μg cm-1h-1). The result proved that NLC encapsulate OS had better delivery system compared to OS extract. In lipolysis study, OS-NLC was found to stimulate the release of glycerol in 3T3-L1 adipocytes cells. Taken together, the optimal OS-NLC formulation had efficiently enhanced penetration into skin and improved the lipolysis activity in adipocyte cell.