Development of Spray-Dried Micelles, Liposomes, and Solid Lipid Nanoparticles for Enhanced Stability

Objectives: Micelles, liposomes, and solid lipid nanoparticles (SLNs) are promising drug delivery vehicles; however, poor aqueous stability requires post-processing drying methods for maintaining long-term stability. The objective of this study was to compare the potential of lipid-based micelles, liposomes, and SLNs for producing stable re-dispersible spray-dried powders with trehalose or a combination of trehalose and L-leucine. This study provides novel insights into the implementation of spray drying as a technique to enhance long-term stability for these lipid-based nanocarriers. Methods: Aqueous dispersions of LDV-targeted micelles, liposomes, and SLNs loaded with paclitaxel (PTX) were converted into re-dispersible powders using spray drying. The physicochemical properties of the nanocarriers were determined via scanning electron microscopy (SEM), Karl Fischer titration, differential scanning calorimetry (DSC), and dynamic light scattering (DLS). Short-term stability of all nanocarrier formulations was compared by measuring particle size, polydispersity index (PDI), and paclitaxel retention over 7 days at room temperature and at 4 °C. Results: Paclitaxel-loaded micelles, liposomes, and SLN formulations were successfully converted into well-dispersed spray-dried powders with acceptable yields (71.5 to 83.5%), low moisture content (<2%), and high transition temperatures (95.1 to 100.8 °C). SEM images revealed differences in morphology, where nanocarriers spray-dried with trehalose or a combination of trehalose and L-leucine produced smooth or corrugated particle surfaces, respectively. Reconstituted spray-dried nanocarriers maintained their nanosize and paclitaxel content over 7 days at 4 °C. Conclusions: The results of this study demonstrate the potential for the development of spray-dried lipid-based nanocarriers for long-term stability.