Yes, the optimal N/P ratio can vary depending on the cationic lipid. Stearylamine, being a primary amine, interacts differently with siRNA compared to quaternary ammonium lipids like DOTAP. In most cases, you may need a slightly higher N/P ratio with stearylamine to achieve similar complexation and transfection efficiency. A short titration range (e.g., N/P 2–10) is often helpful to identify the optimal condition in your system. Hope this helps!

Hi!

Yes, the optimal N/P (nitrogen to phosphate) ratio indeed varies depending on the type of cationic amide used in liposomal siRNA delivery systems, as it is influenced by the molecular structure, charge density, hydrophobicity, and buffering capacity of the cationic lipid or polymer. Cationic amides such as DOTAP, DC-Chol, or more complex lipid-like materials (lipidoids) interact differently with the negatively charged phosphate backbone of siRNA. For example, DOTAP often shows optimal transfection efficiency at an N/P ratio of ~3–5, whereas lipidoids like C12-200 may require higher N/P ratios (e.g., 6–10) to form stable, compact lipoplexes and ensure endosomal escape. The variation is due to differences in protonation state at physiological pH, lipid packing, and the resulting liposome surface charge (zeta potential), all of which affect cellular uptake, protection from nucleases, and release of siRNA. Hence, the N/P ratio must be empirically optimized for each cationic amide to balance complex stability, toxicity, and gene silencing efficacy.

Let me know if any further doubts are there related to cationic lipids and nucleic acid drug deliveries. I would like to share my experience with you.

Thank you for your response. I have reviewed several papers regarding the N/P ratio for liposome formulations, and most of the data available focus on DOTAP-based systems. Is there any approach you would recommend to help narrow down a suitable N/P ratio range for my own liposome system? Also, is stearylamine a suitable lipid for complexing with siRNA?