Flow reactor for preparation of lipid nanoparticles via temperature variations

Abstract: Lipid nanoemulsions and nanosuspensions are used as flavor carriers and bubble stabilizers in soft drinks and foods, as well as delivery vehicles for lipophilic drugs in pharmaceutics. Common techniques for their formation are the high-pressure and ultrasonic homogenizers. These techniques dissipate most of the input energy, which results in excessive heating and generation of free radicals that might modify sensitive ingredients. Low energy methods are also used in some applications, but they have specific limitations restricting their universal use. In the current study, we propose an alternative approach - a flow reactor with a variable temperature, which utilizes the lipids' polymorphic transitions to induce spontaneous fragmentation of the lipid microparticles into nanoparticles. The reactor allows us to obtain emulsions or suspensions with particle diameters tunable between 20 and 800 nm when appropriate surfactants, temperature profiles, and flow rates are applied. The fragmentation is comparable to that in a high-pressure homogenizer at ca. 500 bars or higher, without creating emulsion overheating or cavitation typical for the conventional methods. The flow reactor can be scaled up to industrial applications using simple scaling rules.