Sirolimus nano liposomes: Optimization of sirolimus nano liposomes prepared by modified ethanol injection method using response surface methodology

Abstract

The aim of the present study was to apply experimental design methodology in the development and optimization of sirolimus liposomes employing a modified ethanol injection method. Dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Chol) as well as dioleoylphosphoethanolamine (DOPE) were utilized in the preparation of liposomes. Particle size (PS), encapsulation efficiency percent (EE%) and cumulative percent of drug release in 24 h (D24h) were investigated. Analysis of drug was performed using a validated RP-HPLC method. The response surface methodology, utilizing the polynomial equations, graphical plots and response optimization were used to evaluate the effects of each formulation variables on the responses and prediction of the optimal formulation for sirolimus liposomes as well. DPPC/Chol and DOPE/DPPC molar ratios were selected as independent variables and correspondingly, results of PS, EE% and D24h were considered as responses of the experimental design. Results ranges for PS, EE% and D24h were 89-200 nm, 63.3-97.4 % and 13.18-22.86 %, respectively. The effects of DPPC/Chol and DOPE/DPPC molar ratios on D24h were significant, but in the case of PS and EE%, only the DPPC/Chol molar ratio had a significant effect (P< 0.05). Therefore based on the obtained results, the ethanol injection method could be a rapid, simple and inexpensive method for the preparation of liposomes. © ECV. Editio Cantor Verlag, Aulendorf (Germany).