The current methods for treatment of
cancers are inadequate and more specific methods such as gene therapy are in progress. Among different vehicles, cationic
liposomes are frequently used for delivery of genetic material. This investigation aims to prepare and optimize
DOTAP cationic
liposomes containing an antisense oligonuclotide (AsODN) against
protein kinase C alpha in non-small cells
lung cancer (NSCLC). To perform this investigation, two different methods of
ethanol injection and thin film hydration were used to prepare AsODN-loaded
DOTAP liposomes. The formulated
liposomes were then evaluated for their morphology, particle size, zeta potential and encapsulation efficiency, and the best formulation was chosen. In-vitro growth inhibitory effect of encapsulated ODN on A549 cells were evaluated by MTT and colonogenic assay. The physical and serum stability of liposomal ODN were also evaluated. Thin film hydration method resulted in large
liposomes that required downsizing by extrusion with an encapsulation efficiency of 13%.
Ethanol injection, in a single step gave
liposomes with a small size of 115 nm and an encapsulation efficiency of around 90% which were physically stable for 6 months. The optimized
liposome could protect
oligonucleotides from degradation by nuclease. Cell studies showed a 20% sequence-specific inhibition of cell growth in MTT assay and revealed an LC50 of 103 nM in colonogenic studies. In conclusion,
ethanol injection was able to provide suitable
liposomes from the permanently charged
DOTAP. Also the resulted
liposomes were able to inhibit the growth of
lung cancer cells.