Effect of sucrose as a lyoprotectant on the integrity of paclitaxel-loaded liposomes during lyophilization

Abstract

Context: The stability of liposomes in the form of dispersion is a major concern due to drug leakage and fusion or aggregation. The stability can be improved by lyophilization, but the stress induced by the lyophilization process can affect the integrity of liposomes.Objective: The objective of this study was to evaluate the lyoprotective effect of sucrose on drug leakage and vesicle size of paclitaxel-loaded liposomes during the lyophilization process.Materials and methods: Paclitaxel-loaded liposomal dispersions were prepared with sucrose at several lipid–sugar ratios, and internal–external sugar ratios, and then lyophilized. The entrapped paclitaxel content and vesicle size were monitored before and after lyophilization. The stability of the formulation was evaluated at 5 and 25 °C.Results: A significant increase in free paclitaxel and vesicle size was observed with the liposomes lyophilized without sucrose. Inclusion of sucrose in the formulation significantly reduced the free paclitaxel concentration and minimized the changes in vesicle size. The extent of protection improved further when sucrose was also present in the internal portion of the bilayer. The lyophilized formulation was stable at 5 °C for 3 months.Discussion: A significant (p < 0.05) correlation was observed between free paclitaxel content and the average diameter of the liposomes with respect to sucrose concentrations in the formulation. Sucrose protected the liposomes from drug leakage and aggregation/fusion induced by the lyophilization process in a concentration dependent manner.Conclusion: The integrity of paclitaxel-loaded liposomes was preserved during lyophilization by optimal levels of lyoprotectant sucrose in the formulation.