miRNA-21 Inhibitor-Loaded Cationic Liposomes Development using the Quality by Design Approach

The success of efficiently delivering genetic material to target cells depends on developing an appropriate vector. Among the variety of nanocarriers used for gene therapy, cationic liposomes are the most investigated for delivering genetic material in different forms of cancer. Cationic liposomes contain lipids with positively charged head groups that form electrostatic bonds with the negatively charged phosphate group of nucleic acids, ensuring efficient loading of the genetic material. The aim of this study was the development and in vitro characterization of liposomal formulations for genetic material delivery using the Quality by Design (QbD) approach. We have employed the Design of Experiments (DoE) methodology to study the impact of selected formulation factors on the quality of the proposed non-viral vectors. Among the varied factors, the ones that had an impact on the responses were the total lipid concentration and cationic lipid concentration. Two liposomal formulations with adequate critical quality attributes (CQAs) were selected for miRNA-21 inhibitor encapsulation. We continued with the in vitro evaluation on lung cancer cell line. Fluorescence microscopy helped visualize the internalization of all liposomal formulations and apoptotic effects. Finally, we evaluated the cellular viability and migration events after treatment with the cationic liposomes. miRNA-21 is a well-documented oncogene with a key role in cancer pathogenesis, thus a potential target for new cancer therapies. In this study cationic liposomes loaded with miRNA-21 inhibitor (miR-21inh) were developed and evaluated for their targeting ability in lung cancer cells. miR-21inh liposomes were successfully internalized in lung cancer cells, leading to cellular apoptosis. image