Gadolinium-Loaded Nanoparticles Engineered from Microemulsion Templates

ABSTRACT

Microemulsions (oil-in-water) have been used as templates to engineer stable emulsifying wax and Brij 72 (polyoxyl 2 stearyl ether) nanoparticles. The technique is simple, reproducible, and amenable to large-scale production of stable nanoparticles having diameters below 100 nm. Investigation of the process variables showed that the amount of surfactant used in the preparation of microemulsion templates had the greatest influence on the microemulsion window, as well as the properties and stability of the cured nanoparticles. Emulsifying wax and Brij 72 nanoparticles (2 mg/mL) made with 3 mM polyoxyl 20 stearyl ether and 2.3 mM polysorbate 80, respectively, were the most stable based on retention of nanoparticle size over time. Gadolinium acetylacetonate (GdAcAc), a potential anticancer agent for neutron capture therapy (NCT), was entrapped in stable nanoparticles. The apparent water solubility of GdAcAc was increased more than 2000-fold by entrapment into nanoparticles. The entrapment efficiency of GdAcAc was about 100% for emulsifying wax nanoparticles and 86% for Brij 72 nanoparticles, as determined by gel permeation chromatography (GPC). Elution profiles were obtained with light scattering (counts per second) to detect nanoparticles and ultraviolet (UV) absorption of GdAcAc at 288 nm. Challenges of these cured nanoparticles in biologically relevant media such as 10% fetal bovine serum, 10 mM phosphate-buffered saline, 150 mM NaCl, and 10% lactose at 37°C for 60 min demonstrated that these nanoparticles are stable. The ease of preparation of these very small and stable nanoparticles, and the ability to entrap lipophilic drugs such as GdAcAc with high efficiency, suggested that these systems may have potential in cell targeting, especially for specific delivery to tumor cells for NCT.

• Brij 72
• Emulsifying wax
• Gadolinium acetylacetonate
• Neutron capture therapy
• Polysorbate