Calixaren as novel gene vector formulated within spray-dried inhalable powders

The works illustrates the innovative use of calixarenes as gene vectors in the formulation of inhalable powders aimed at delivering genetic material. Calixarenes have the capability to bind to genetic material and facilitate cell transfection, offering a promising alternative to traditional lipid nanoparticles (LNP). Results show that these compounds can successfully condense DNA through electrostatic interactions, and spray drying is a suitable production technique to include them in composite respirable microparticles. The formulation development combined Trehalose and Leucine to optimize the aerodynamic properties necessary for effective delivery and DNA lung deposition. Leucine plays a significant role in improving the dispersion characteristics of the powder (FPF of 46.5%). The DNA was intact after the production process and still complexed to the vector. The redispersed powders were able to transfect A549 cells expressing GFP (up to 25% of the total cells). This project reflects a significant advancement in the design of respiratory gene delivery systems, showing high transfection efficiency of this platform highlighting the potential of calixarene-based systems in therapeutic applications.