Liposomes for enhanced intracellular delivery of therapeutics through inhalation: design and physicochemical characterization

With their ability to encapsulate therapeutics and release their content at the desired time, liposomes provide a valuable platform for the treatment of a variety of diseases. Notwithstanding their impressive advantages, the administration modality plays a not less important role in targeting efficiency and side effect reduction, as well as patient comfort. In this regard, a promising alternative to intravenous administration is represented by pulmonary administration by inhalation.1,2 We developed liposomes using the main component of pulmonary surfactant (DPPC) as a major substituent to improve the biocompatibility of the entire system and ensure better interaction with the lung surfactant membrane, which is the main barrier that liposomes need to overcome while being pulmonary administrated. Liposomes with different compositions have been designed to understand how each lipid (DPPC, DOTAP, and cholesterol) affects the physicochemical properties of the system itself. This was done by combining several techniques, such as DSC, DLS and SAXS. The results obtained revealed that DOTAP and cholesterol addition affect liposome size, as well as lipid system transition temperature. Preliminary tests have been performed to encapsulate a CSC-targeting DNA aptamer (AP-9R) that suppresses tumorigenesis, cancer progression and angiogenesis in lung cancer.3 Understanding how the different lipids affected the physicochemical properties of lipid nanocarriers, can benefit the development of new strategies for the delivery of oligonucleotide therapeutics, providing a scientific platform for future clinical approaches.