The size, shape and surface properties of pharmaceutical nanoparticles may be tailored with colloid engineering for controlled release and enhanced dissolution behavior. Stable low molecular weight and protein nanoparticles (50 to 500 nm) may be utilized in parenteral, subcutaneous and pulmonary delivery to increase drug potency and the bioavailability, while reducing side effects. The nanoparticles may be formed by precipitation with an antisolvent (either a liquid or supercritical CO2), flash nanoprecipitation (Prudhomme and coworkers), spray freeze drying and thin film freezing. The final particle morphology in the therapeutic dosage form often depends as much on the method of recovery of the nanoparticles from the precipitator as on the precipitation method.

For poorly water soluble drug nanoparticles, high surface areas and stable amorphous polymorphs enhance thermodynamic and kinetic properties of dissolution. The nanoparticles may be coated with surfactants and targeting agents to: (1) control particle nucleation and growth to control the size and morphology, and (2) facilitate in vitro and in vivo wetting and dissolution behavior in the GI tract, bloodstream or lungs and (3) enhance targeting of tumors. For pulmonary delivery, a novel concept is presented for the formation of stable suspensions composed of very low density flocs of rod-shaped drugs in hydrofluoroalkane propellants for pressurized meter dose inhalers (pMDI), and for templating the flocs to achieve high fine particle fractions in the deep lungs.

Given the rapid discovery of therapeutic peptides and monoclonal antibodies, there is great interest in less invasive delivery methods than intravenous administration. Highly concentrated dispersions of protein particles are described for subcutaneous injection and pulmonary administration, as an alternative to protein solutions. Protein nanoparticles with unusually high stability may be precipitated with novel spray freezing and thin film freezing processes, by minimizing the time of exposure of protein to air-water and ice-water interfaces.

The future offers exciting opportunities in colloid engineering for combined imaging and therapy to deliver drugs more selectively to intended targets. A goal is to design nanocomposites composed of magnetic and/or optical inorganic nanoparticles with sufficient contrast for imaging (mri, optical coherence tomography, photoacoustic) and high drug payloads.