Title:Liposomal Doxorubicin Delivery Systems: Effects of Formulation and Processing Parameters on Drug Loading and Release Behavior
VOLUME: 13 ISSUE: 7
Author(s):Zahra Ali Mohammadi, Seyed Foad Aghamiri, Ali Zarrabi and Mohammad Reza Talaie
Affiliation:Department of Chemical Engineering Faculty of Engineering, University of Isfahan, Hezar-Jerib Ave., Isfahan, 81746-73441, Iran.
Keywords:Active loading, cancer therapy, cholesterol, controlled released, doxorubicin, liposome.
Abstract:Liposomes can serve as promising carriers for targeting delivery and controlled
release of anti-cancer drugs. Doxorubicin-loaded liposomes have achieved
enhanced efficacy in some solid tumors due to EPR effect with prolonged circulation
and reduced toxicity. In this study the effects of liposomal structure have been investigated
on the loading efficiency and controlled release behavior. Liposomes with
various compositions were prepared through a thin film hydration method, and extruded
to large unilamellar vesicles (LUVs) with mean particle size (Z ave~ 100 nm)
by high-pressure extrusion technique. Then, doxorubicin was loaded into liposomes
using remote active loading strategy. The loading efficiency and drug release behavior
were evaluated using various parameters such as medium pH, liposome compositions
and cholesterol concentrations. Liposomes prepared with different compositions showed high levels
of drug encapsulation. Drug loading efficiencies (>90%) achieved with high final drug/lipid ratio
(0.18-0.2). Faster release was observed at pH 5.5 when compared to pH 7.4 for all formulations. The
fastest release rate was observed for unsaturated lipid (<48hr) and the slowest release rate was observed
for saturated lipids with high phase transition temperature such as 1, 2-distearoylphosphatidylcholine
(DSPC) and hydrogenated soy phosphatidylcholine (HSPC) (10-18 days). The sustained release was observed
for liposomal formulations containing cholesterol. In conclusion, we have demonstrated that
drug release rate could be controlled by manipulating the composition of liposomal structures.
