Development of nobiliside A loaded liposomal formulation using response surface methodology.
To reduce the hemolysis and toxicity of nobiliside A (Nob), liposomes were used as a carrier in this study. Response surface methodology (RSM) based on central composite rotatable design (CCRD) was applied for formulation optimization. Phosphatidyl choline (PC) proportion, cholesterol (CH) proportion, and lipids/drug ratio were selected as the independent variables while the encapsulation efficiency (EE) and hemolytic rate (HR) of the liposomes as the dependent variables. The results indicated CH proportion and lipids/drug ratio were the major contributing variables for EE and PC/CH ratio was the major contributing variables for HR. The optimum formulation of Nob liposomes, in which PC proportion of 2% (w/v), CH proportion of 0.9% (w/v), and lipids/drug ratio (w/w) of 40, had higher EE (>95%) and lower HR (<1% at the concentration of 80 microg mL(-1)) with spherical shape and uniform sizes. The intravenous LD50 increased to 9.5 mg kg(-1) compared to 4.1 mg kg(-1) of Nob solution. In conclusion, the liposome was a safety and effective carrier for intravenous Nob.
Xiong
Yang
Y
Department of Pharmaceutical Science, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Guo
Dan
D
Wang
Lili
L
Zheng
Xiaoli
X
Zhang
Yue
Y
Chen
Jianming
J
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D007928:Lethal Dose 50; D008081:Liposomes; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D010316:Particle Size; D011817:Rabbits; D012503:Saponins / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D013499:Surface Properties; D014465:Ultrasonics
C515791:3-O-xylopyranosylholosta-7,9(11),22,24-tetraene-3,17-diol; D008081:Liposomes; D012503:Saponins