This paper presents the development of magnetic lipid nanoparticles that could serve as controlled delivery vehicles for releasing encapsulated drugs in a desired manner. The nanoparticles are composed of multiple drugs in lipid matrices, which are solid at body temperature and melt around 45°C to 55°C. In addition, super-paramagnetic γ-Fe2O3 particles with sizes ranging from 5 to 25 nm are surface modified and dispersed uniformly in the lipid nanoparticles. In the prototype demonstration, lipid nanoparticles with average sizes between 100 and 180 nm were fabricated by high-pressure homogenization at elevated temperatures. When exposed to an alternating magnetic field of 60 kA/m at 25 kHz, a solution containing 2 g/L encapsulated γ-Fe2O3 particles showed a temperature increase from 37°C to 50°C in 20 min. Meanwhile, the dissipated heat melted the surrounding lipid matrices and resulted in an accelerated release of the encapsulated drugs. Within 20 min, approximately 35% of the encapsulated drug molecules were released from the lipid nanoparticles through diffusion. As such, the presented lipid nanoparticles enable a new scheme that combines magnetic control of heating and drug delivery, which could greatly enhance the performance of encapsulated drugs.
Drug delivery Hyperthermia Nanoparticles Solid lipid nanoparticles Homogenization Magnetic heating Controlled release
The demonstrated systems were fabricated in the ESS Microfabrication Lab at National Tsing Hua University, Taiwan. This work was supported in part by the National Science Council of Taiwan under Contract no. NSC 96-2221-E-007-116-MY3.