Evaluation of the drug loading capacity of different lipid nanoparticle dispersions by passive drug loading.

When using lipid nanoparticles as drug carrier system it is important to know how much drug can be loaded to the nanoparticles. The mainly used drug loading procedure is an empirical approach dissolving the drug in the liquid lipid during preparation of the nanoparticles. This approach does not necessarily lead to the truly loadable amount, as the lipid can, e.g. be overloaded, in particular when it is processed in the heat. In this work, a different procedure, passive drug loading, was evaluated to determine the drug loading capacity of various lipid nanoparticles (supercooled trimyristin emulsion droplets, solid trimyristin nanoparticles, tristearin nanoparticles in the α-modification and cholesteryl myristate nanoparticles in the supercooled smectic as well as in the crystalline state). The nanoparticle dispersions were exposed to eight different model drug compounds (betamethasone-17-valerate, carbamazepine, diazepam, flufenamic acid, griseofulvin, ibuprofen, retinyl palmitate, ubidecarenone) in the bulk state, which varied in partition coefficient and aqueous solubility, and equilibrated over time. The passive loading procedure had no relevant impact on the particle sizes or the physicochemical state of the nanoparticles. The loadable drug amount differed distinctly for the different model compounds and also between the different types of lipid nanoparticles. For most compounds, the loaded amount was much higher than the aqueous solubility. Trimyristin-based dispersions generally had the highest loading capacity, the emulsion usually being equal or superior to the solid trimyristin nanoparticles. For betamethasone-17-valerate, however, solid lipid nanoparticles exhibited by far the highest drug load. The extremely lipophilic model drugs retinyl palmitate and ubidecarenone could not be loaded with the passive approach.