Improvement of membrane stabilizer on the rehydrated reconstruction of spray-dried mannitol-based liposome powder

Abstract

Spray drying is regarded as one of the most economical methods utilized in the production of liposome powder in industry. However, the poor reconstruction of the powder following rehydration imposes constraints on its potential utilization. In this study, three membrane stabilizers, Poloxamer 188 (P188), trehalose (Tre), and Tween 80 (T80) were selected due to their distinct localization behaviors, and their impact on the reconstruction of rehydrated liposomes was discussed. The mannitol-based spray-dried liposome powder with excellent reconstruction was successfully developed. After rehydrating the powder, the particle size (D_h) and polydispersion index (PDI) of mannitol-encapsulated liposome powder (Bla) significantly increase. Although adding leucine improved the dispersion of the powder (Bla/Leu), the increase in D_h and PDI after rehydration was more significant, changed from 172.79 nm and 0.075 for Bla to 459.97 nm and 0.291 for Bla/Leu, the micropolarity and hydrophobicity of membrane also increased, indicating a poorer reconstruction. The addition of extra membrane stabilizers enhanced the stability of the liposomes after rehydration. Specifically, the addition of T80 reduced the changes in D_h and PDI caused by leucine to 118.39 nm and 0.015, while the changes of ANS fluorescence intensity and I₁/I₃ to 178.66 a.u and 0.02. Raman spectroscopy revealed that the addition of membrane stabilizer greatly reduced the disorder of the acyl chain, especially the T80. It could be the embedding mode of T80 on liposomes and its excellent solubilization played the best role. It also showed the best stability in extreme environments such as acidity and ionic strength.

Graphical Abstract