Engineering Optimized Nanostructured Lipid Carriers for Astaxanthin: A Response Surface Methodology Approach

Introduction: The xanthophyll carotenoid astaxanthin is well-known for its potent antioxidant properties, which are superior to those of other antioxidants such as vitamins C and E. However, this highly hydrophobic compound has low solubility and poor oral bioavailability, limiting its efficacy and clinical application. To address these pharmacokinetic challenges, nanostructured lipid carriers (NLC) have been proposed as potential lipid-based drug carriers for the oral delivery of astaxanthin owing to their excellent biocompatibility, stability, and efficient drug loading capacity. Purpose: In this study, we aimed to develop an NLC using cocoa butter and palm oil for astaxanthin encapsulation, and to optimize the nanoformulation by employing Response Surface Methodology (RSM), a statistical approach. Methods: Three-factor Central Composite Design (CCD) in RSM was used to understand the effect of independent variables on response variables. The size, polydispersity index, and encapsulation efficiency of the astaxanthin-loaded NLC were also characterized. Results: Findings of this study indicated that the mass of cocoa butter, palm oil and Tween 80 influenced the particle size, polydispersity index and zeta potential of NLC. The experimental determination of NLC did not differ significantly from the predicted RSM outcomes with size, polydispersity index and zeta potential of 254.42 ± 3.91 nm, 0.38 ± 0.01 and − 30.54 ± 0.85 mV, respectively. This nanoparticulate system showed an excellent astaxanthin entrapment efficiency of 99.69± 0.0003%. Conclusion: The ideal combination of each composition in the NLC formulation yielded nanoparticles with desirable particle size, polydispersity index, and zeta potential for efficient oral delivery of astaxanthin. Plain Language Summary: Astaxanthin is a natural antioxidant that is much stronger than vitamins C and E. However, it does not dissolve well in water and is poorly absorbed when administered orally, which limits its usefulness. To overcome this drawback, this study explored the use of nanostructured lipid carriers (NLC), which are tiny fat-based particles, to improve astaxanthin movement in the body. An NLC formulation was developed using cocoa butter and palm oil. The optimization process was conducted using a statistical method called Response Surface Methodology (RSM) to determine the best combination of ingredients. Different amounts of cocoa butter, palm oil, and a stabilizer (Tween 80) can affect the size, stability, and ability of the particles to hold astaxanthin. The results also showed that the optimized NLC had a small and uniform size (approximately 254 nm), stable dispersion (zeta potential of − 30.54 mV), and highly efficient astaxanthin trapping (99.69%). In conclusion, we successfully developed an NLC formulation that can efficiently carry astaxanthin, potentially improving its absorption and effectiveness when used as a supplement or medicine. Keywords: astaxanthin, nanoformulation, drug delivery, nanostructured lipid carriers, response surface methodology, central composite design