Formulation And Evaluation Of Nanostructured Lipid Carriers (NLCs) Of 20(S)-Protopanaxadiol (PPD) By Box-Behnken Design

Background: 20(S)-Protopanaxadiol (PPD) has a higher anti-wrinkle effect than the other glycone forms of ginsenosides. However, as PPD has low solubility in water and a high molecular weight, it cannot easily penetrate the stratum corneum layer, which is the rate-limiting step of topical skin delivery. Thus, the objective was to enhance the topical skin deposition of PPD using an optimized nanostructured lipid carriers (NLC) formulation. NLC formulations were optimized using a Box-Behnken design.

Materials and methods: NLC formulations were optimized using a Box-Behnken design, where the amount of PDD (X₁), volume of the liquid lipid (X₂), and amount of surfactant (X₃) were set as the independent variables, while the particle size (Y₁), polydispersity index (PDI) (Y₂), and entrapment efficiency (EE) (Y₃) were dependent factors. An in vitro deposition study was performed using Strat-M^® and human cadaver skin, while in vivo skin irritation effect of the NLC formulation was evaluated in humans.

Results: An NLC was successfully prepared based on the optimized formulation determined using the Box-Behnken design. The particle size, PDI, and EE of the NLC showed less than 5% difference from the predicted values. The in vitro deposition of PPD after the application of the NLC formulation on a Strat-M^® artificial membrane and human cadaver skin was significantly higher than that of the controls. Moreover, NLC formulations with and without PDD were not skin irritants in a human study.

Conclusion: An NLC formulation for the topical delivery of PPD was successfully optimized using the Box-Behnken design, and could be further developed to enhance the topical skin deposition of PPD.