Therapeutic nanoparticles with controlled properties enable control over therapeutic outcomes, through drug targeting to specific sites, enhancing cellular uptake, protection against drug inactivation and achieving controlled drug release. Current nanoparticle preparation methods, through mechanical or colloidal processing, have limitations of thermal damage and/or extensive post-processing steps. We have pioneered a pulse heat aerosol reactor (PHAR) method (Venkataraman and Pawar, 2015, US Patent No. US 9066882 B2) for single step processing of heat-sensitive lipids into therapeutic nanoparticles containing payloads of drugs (gefitinib, isoniazid), pDNA and insulin, with layering for controlled release and surface modification for suspension stability. We model multi-solute containing nano-droplet aerosol spray drying to understand mechanisms governing the properties of synthesized nanoparticles.