Duodenal administration of solid lipid nanoparticles loaded with different percentages of tobramycin.

Three types of solid lipid nanoparticles (SLN) containing three different percentages of tobramycin (1.25, 2.50, 5.00%) were prepared (Tobra-SLN), and the in vitro tobramycin diffusion through a hydrophilic/lipophilic membrane was determined. A variable quantity of each of the three SLN types was placed in the donor compartment to achieve the same amount of tobramycin in each case. Tobramycin diffusion varied with the percentage of drug incorporated in SLN: the higher the percentage of tobramycin incorporated, the greater the amount of the drug diffused. In vivo uptake and transport were determined after administering a fixed dose of tobramycin (5 mg/kg) in each of the three types of SLN intraduodenally to rats. At fixed times, blood was sampled from the jugular vein and lymph from the thoracic duct. Lymph and blood were examined by transmission electron microscopy (TEM) analysis to detect the presence, sizes, and shape of SLN. The pharmacokinetic parameters varied considerably with the type of Tobra-SLN: the area under the curve of plasma concentration versus time (AUC) of 1.25% Tobra-SLN was more than five times higher than that of 5.00% Tobra-SLN; the longest residence time was obtained with 1.25% Tobra-SLN; and the clearance of 5.00% Tobra-SLN was fivefold than that of 1.25% Tobra-SLN. This behavior may be related to the differences among the three types of SLN; namely, the number of SLN administered and the mean diameter, the total surface area, and the drug content in each nanoparticle. TEM analysis showed that Tobra-SLNs were targeted to the lymph. Tobra-SLN may act as a reservoir of the drug in the lymphatic system, thereby favoring its sustained release. Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:1085-1094, 2003