Uptake of Nanoparticles by Rat Glomerular Mesangial Cells in Vivo and in Vitro

Abstract

Glomerular mesangial cells play a major role in the structure of capillary loops, generation of mediators of inflammation, and uptake of macromolecules. We demonstrate here that isobutylcyanoacrylate nanoparticles loaded with actinomycin D (ADNP) concentrate in rat mesangial cells in vitro and in vivo, as compared to the free drug (AD). In normal rats injected with 20 µg of ³H-ADNP or ³H-AD, the uptake ratios ³H-ADNP/³H-AD measured in whole kidneys at 30 and 120 min were 2.2 ± 1.0 and 2.3 ± 0.9, respectively. The same ratios calculated for isolated rat glomeruli and tubules, were 4.1 ± 0.5 and 0.8 ± 0.2 at 30 min, and 2.6 ± 0.5 and 0.6 ± 0.3 at 120 min, respectively. In the glomeruli, the absolute uptake of ³H-ADNP corresponded to 7.5 (30 min) and 1.8 (120 min) % I.D./100 mg of protein. In rats with experimental glomerulonephritis, the uptakes of ³H-ADNP and ³H-AD by the glomeruli were 6.9 and 4.0 times higher than in normal rats, respectively. In vitro experiments demonstrated up to 5 times higher uptake by glomerular mesangial cells than by epithelial cells. Uptake was maximum after 60 min, higher at 37°C than at 4°C, dependent on the presence of fresh serum and inhibited by cytochalasin-B. Drug targeting by nanoparticles is thus possible to renal cells involved in inflammatory processes, especially mesangial cells and macrophages. Nanoparticles could also be useful for lowering drug concentration in tubular cells, to reduce any tubular toxicity. Targetting of the mesangial cells is of particular interest for drugs such as corticosteroids capable of reducing glomerular inflammation in various pathological conditions.