(519d) Synthesis of Nanoparticles of Magnetite and Drug-Polymer Complexes Using a Multi-Inlet Vortex Mixer

Functional nanoparticles that have well-defined size distributions and are colloidally stable in aqueous media are important for biomedical applications. Clusters of superparamagnetic particles are particularly interesting as magnetic resonance imaging (MRI) contrast agents. For drug nanoparticles, control of the particle size distribution is very important in biological systems for cellular uptake and targeted delivery. Thus, development of a method to control the size of sterically stabilized nanoparticles is needed. We have used a multi-inlet vortex mixer (MIVM)[1,2] to create clusters of superparamagnetic particles of magnetite and to create drug-polymer complexes. In the MIVM, particle formation occurs by the rapid mixing of an organic active and a stabilizing amphiphilic polymer, dissolved in an organic solvent, with an antisolvent to create solutions with high supersaturation values. To produce nanoparticles of homogeneous particle size, the mixing time has to be lower than the nucleation and growth time scale.

The MIVM process was used to make clusters comprised of hydrophobically modified magnetite nanoparticles (diameter ~10 nm) dispersed in Tetrahydrofuran (THF) stabilized with an amphiphilic polymer, Pluronics F-127 (a triblock of Poly (ethylene oxide-b-propylene oxide-b-ethylene oxide)). Clusters of these magnetite nanoparticles were formed with hydrodynamic diameters ranging from 60-230 nm in aqueous media. The control of the composition of these clusters and the response of the cluster colloidal stability to an external magnetic field will be discussed.

The MIVM process was also used to encapsulate the antibiotic doxycycline using an amphiphilic polymer designed to achieve intracellular delivery of the antibiotic and to increase the drug loading content. Doxycycline is water-soluble and so it was complexed first with cholic acid to form the water-insoluble doxycycline-cholate salt that was soluble in THF. Particles of this salt were precipitated in water and encapsulated with a pentablock polymer (Poly(caprolactone)-poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)-poly(caprolactone)). After the nanoparticles were formed, they were dialyzed to remove organic solvent and unimer chains and were then characterized by dynamic light scattering and electron microscopy. Nanoparticles with number average hydrodynamic diameters in the range 50?200 nm were formed. The control of drug loading in these particles will be discussed along with cell uptake studies and the pharmacokinetics of antibiotic release.

References:

1.Liu, Y; Cheng, C; Liu, Y; Prud'homme, RK; Fox, RO. Mixing in a multi-inlet vortex mixer (MIVM) for flash nano-precipitation. Chemical Engineering Science 2008, 63, 2829-2842.

2.Johnson, BK; Prud'homme, RK. Mechanism for rapid self-assembly of block copolymer nanoparticles. Phys. Rev. Lett. 2003, 91, 118302:1-4.