Duodenal Administration of Solid Lipid Nanoparticles Loaded with Different Percentages of Tobramycin ROBERTA CAVALLI, 1 ALESSANDRO BARGONI, 2 VALERIO PODIO, 3 ELISABETTA MUNTONI, 4 GIAN PAOLO ZARA, 4 MARIA ROSA GASCO 1 1 Dipartimento di Scienza e Tecnologia del Farmaco, Universita ` degli Studi di Torino, Via P. Giuria 9, I-10125 Torino, Italy 2 Dipartimento di Fisiopatologia Clinica, Universita ` degli Studi di Torino, Via Genova 9, I-10125 Torino, Italy 3 Dipartimento di Medicina Interna, Universita ` degli Studi di Torino, Via P. Giuria 9, I-10125 Torino, Italy 4 Dipartimento di Anatomia, Farmacologia e Medicina Legale, Universita ` degli Studi di Torino, Via P. Giuria 13, I-10125 Torino, Italy Received 11 March 2002; revised 20 November 2002; accepted 22 November 2002 ABSTRACT: 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 clearence 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. ß 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:1085– 1094, 2003 Keywords: solid lipid nanoparticles; tobramycin; enteral absorption; pharmacoki- netics parameters; lymphatic uptake INTRODUCTION In recent years, much effort has been made to achieve lymphatic targeting of drugs using colloidal carriers. Many particulate systems, such as emulsions, 1 liposomes, 2,3 and polymeric nano- particles 4–6 have been studied for this purpose. Colloidal carriers can enhance drug lymphatic targeting using different administration routes, such as intramuscular, subcutaneous, intraper- itoneal, or peroral. 7 Lipophilic compounds are mainly transported through the lymphatic system and reach the systemic circulation via the thoracic JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 92, NO. 5, MAY 2003 1085 Correspondence to: Maria Rosa Gasco (Telephone: 011- 6707825; Fax: 011-6707687; E-mail: mariarosa.gasco@unito.it) Journal of Pharmaceutical Sciences, Vol. 92, 1085–1094 (2003) ß 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association