Influence of formulation parameters on gadolinium entrapment and tumor cell uptake using folate-coated nanoparticles

Emulsifying wax and polyoxyl 2 stearyl ether (Brij 72) nanoparticles (2 mg/ml) containing high concentrations of gadolinium hexanedione (GdH) (0-3 mg) have been engineered from oil-in-water microemulsion templates. Solid nanoparticles were cured by cooling warm microemulsion templates (prepared at 55 degreesC) to room temperature in one vessel. Nanoparticles were characterized by transmission electron microscopy (TEM), photon correlation spectroscopy (PCs) and gel permeation chromatography (GPC). To obtain folate-coated nanoparticles, a folate ligand was added to either the microemulsion templates or nanoparticle suspensions at 25 degreesC. Since the concentration of Gd in the tumor is critical to the success of Gd-neutron capture therapy (NCT), the effects of various formulation factors on GdH entrapment in nanoparticles as well as tumor-targeting were studied. GdH entrapment in nanoparticles was affected mostly by the method of GdH incorporation and surfactant concentration used in preparing the microemulsion templates. Cell uptake studies were carried out in KB cells (human nasopharyngeal epidermal carcinoma cell line). The method of adding folate ligand to the formulations did not significantly affect nanoparticle cell uptake (P > 0. 11; t-test). However, the concentration of folate ligand added to nanoparticles had the greatest influence on nanoparticle uptake (P < 0.0 1; t-test). The results showed that GdH entrapment and cell uptake were optimized and suggested that engineered folate-coated nanoparticles may serve as effective carrier systems for Gd-NCT of tumors. (C) 2002 Elsevier Science B.V. All rights reserved.