(599s) Ritonavir Nanoparticles Stabilized By Amphiphilic Block Copolymers

Authors: 
Davis, R. M., Virginia Tech
Balasubramaniam, S., Virginia Tech
Kayandan, S., Virginia Tech
Riffle, J. S., Virginia Tech

For the treatment of diseases such as Human Immunodeficiency virus, it is important to formulate drugs so that they are released in a controlled and sustained manner.  Polymer-encapsulated drug nanoparticles are particularly interesting due to the enhanced properties that result from interactions between the polymer carrier and the drug and from a reduction in particle dimensions. This work concerns the fabrication and characterization of nanoparticles of the antiretroviral drug, ritonavir which were sterically stabilized by amphiphilic block copolymers comprised of poly(ethylene oxide-b-butylene oxide) and poly(ethylene oxide-b-D,L-lactide). The nanoparticles were formed under turbulent conditions in a multi-inlet vortex mixer. Particles with intensity average hydrodynamic diameters less than 100 nm with narrow polydispersity indices were measured by dynamic light scattering. Particle size distributions with single peaks were achieved by adding homopolymers of either poly(L-lactide) or poly(butylene oxide) that were hydrophobic and hence facilitated the nucleation of the nanoparticles. Ritonavir drug loadings greater than 20 wt% and encapsulation efficiencies ~ 70-80% were attained. The ritonavir was mostly amorphous in the nanoparticles as shown by differential scanning calorimetry and powder X-ray diffraction experiments. Moreover, these nanoparticles were colloidally stable under simulated physiological conditions (phosphate buffered saline containing 1% bovine serum albumin, T = 37°C) for more than 24 hours.