Disclosed herein are nanoparticles comprising a lipid core comprising a sterol； and a complex comprising a cationic agent and a therapeutic agent, wherein the complex is encapsulated within the lipid core. Methods to produce the nanoparticle comprise: combining a cationic agent, a therapeutic agent, and a first water-immiscible solvent with a first aqueous solution, thereby forming a mixture comprising a complex comprising the cationic agent and the therapeutic agent； combining the mixture with a second waterim-miscible solvent, thereby forming an aqueous phase and an organic phase, and separating the organic phase comprising the complex； combining the organic phase comprising the complex with a sterol and a first water-miscible organic solvent； and dispersing the complex in a second aqueous solution to form a herein disclosed nanoparticle. Methods for treating a disease and for reducing nanoparticle burst rate are also disclosed.
