Ethanol injection method for hydrophilic and lipophilic drug-loaded liposome preparation

Abstract

In this article, a hydrophobic (beclomethasone dipropionate; BDP) and a hydrophilic (cytarabine; Ara-C) drugs have been encapsulated in liposomes in order to be administered via the pulmonary route. For this aim, a liposome preparation method, which is easy to scale up, the ethanol injection method, has been selected. The effects of critical process and formulation parameters have been investigated. The drug-loaded liposomes were prepared and characterized in terms of size, zeta potential, encapsulation efficiency, release study, cell uptake, and aerodynamic behavior. Small multilamellar vesicles, with sizes ranging from about 80 to 170 nm, were successfully obtained. Results indicated a significant influence of phospholipid and cholesterol amounts on liposome size and encapsulation efficiency. The higher encapsulation efficiencies were about 100% for the hydrophobic drug (BDP) and about 16% for the hydrophilic one (Ara-C). The in vitro release study showed a prolonged release profile for BDP, in contrast with Ara-C, which was released more rapidly. The cell-uptake test revealed that fluorescent liposomes have been well internalized into the cytoplasm of SW-1573 human lung carcinoma cells, confirming the possibility to use liposomes for lung cell targeting. Nebulized Ara-C and BDP liposomes presented aerodynamic diameters compatible with deep lung deposition. In conclusion, the elaborated liposomes seem to be promising carriers for both Ara-C and BDP pulmonary delivery.

Keywords::

• Liposomes
• ethanol injection method
• nanoprecipitation
• beclomethasone dipropionate
• cytarabine
• pulmonary
• nebulization

Acknowledgments

SW-1573 carcinoma lung cells were kindly given by Dr. Lars-Peter Jordheim, PhD (INSERM U590, Faculté de Médecine Rockefeller, Univesité lyon 1). The authors are grateful to Mr. Serge Buathier for his helpful assistance in performing transmission electron microscopy characterization. Equal contributions were made by authors CJ-M and RD.

Declaration of interest

The authors report no conflicts of interest. This study is an academic work done at the University Claude Bernard Lyon 1 in France. No external financial or scientific support has been provided for the achievement of this work.