Pharmaceutical Research

, Volume 11, Issue 8, pp 1160–1165 | Cite as

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

  • Luc Manil
  • Jean-Claude Davin
  • Charles Duchenne
  • Christine Kubiak
  • Jacqueline Foidart
  • Patrick Couvreur
  • Philippe Mahieu


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.

nanoparticles polyalkylcyanoacrylate endocytosis mesangial targetting kidney 


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  1. 1.
    D. Schlondorff. The glomerular mesangial cell: an expanding role for a specialized pericyte. Faseb J 1:272–281 (1987).Google Scholar
  2. 2.
    J. R. Sedo, S. W. Carey and S. N. Emancipator. Immune complexes bind to cultured rat glomerular mesangial cells to stimulate superoxide release: Evidence for an FC receptor. J. Immunol. 138:3751–3757 (1987).Google Scholar
  3. 3.
    L. Baud, J. Hagege, J. Sraer, E. Rondeau, J. Perez and R. Ardaillou. Reactive oxygen production by rat glomerular mesangial cells during phagocytosis is associated with stimulation of lipoxygenase activity. J. Exp. Med. 158:1836–1852 (1983).Google Scholar
  4. 4.
    D. H. Lovett and R. B. Sterzel: Cell culture approaches to the analysis of glomerular inflammation. Kidney Int. 30:246–254 (1986).Google Scholar
  5. 5.
    P. Couvreur and C. Vauthier. Polyalkylcyanoacrylate as drug carrier: present state and perspectives. J. Control. Rel. 17:187–188 (1991).Google Scholar
  6. 6.
    P. Couvreur, B. Kante, M. Roland and P. Speiser. Adsorption of antineoplastic drugs to polyalkylcyanoacrylate nanoparticles and their release characteristics in a calf serum medium. J. Pharm. Sci. 68:1521–24 (1979).Google Scholar
  7. 7.
    P. Couvreur, B. Kante, L. Grislain, M. Roland and P. Speiser. Toxicity of polyalkylcyanoacrylate nanoparticles. II: Doxorubicin-loaded nanoparticles. J. Pharm. Sci. 71:790–792 (1982).Google Scholar
  8. 8.
    L. Manil, L. Roblot-Treupel and P. Couvreur. Isobutyl cyanoacrylate nanoparticles as a solid phase for an efficient immunoradiometric assay. Biomaterials 7:212–216, (1986).Google Scholar
  9. 9.
    C. Kubiak, L. Manil and P. Couvreur. Sorptive properties of antibodies onto cyanoacrylic nanoparticles. Int. J. Pharm. 41:181–187 (1988).Google Scholar
  10. 10.
    F. Brasseur, P. Couvreur, B. Kante, L. Deckers-Passau, M. Roland, C. Deckers and P. Speiser. Actinomycin D adsorbed on polymethylcyanoacrylate nanoparticles: increased efficiency against an experimental tumor. Eur. J. Cancer 16:1441–1445 (1980).Google Scholar
  11. 11.
    B. Kante, P. Couvreur, V. Lenaerts, P. Guiot, M. Roland, P. Baudhuin and P. Speiser. Tissue distribution of L (3H) actinomycin D adsorbed on polybutylcyanoacrylate nanoparticles. Int. J. Pharm. 7:45–53 (1980).Google Scholar
  12. 12.
    P. Mahieu and R. J. Winand. Chemical structure of tubular and glomerular basement membranes of human kidney. Isolation, purification, carbohydrate and amino-acid composition. Eur. J. Biochem. 12:410–417 (1970).Google Scholar
  13. 13.
    O. H. Lowry, N. J. Rosenbrough, A. L. Farr, and R. J. Randall. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193:265–272 (1951).PubMedGoogle Scholar
  14. 14.
    F. B. Kingsbury and C. P. Clarck. The rapid determination of albumin in urine. J. Lab. Clin. Med. 11:981–986 (1926).Google Scholar
  15. 15.
    J. B. Foidart, C. A. Dechenne, P. R. Mahieu, C. E. Creutz and J. De Mey. Tissue culture of normal rat glomeruli. Isolation and morphological characterization of two homogeneous cell lines. Invest. Cell Pathol. 2:15–26 (1979).Google Scholar
  16. 16.
    G. T. Schreiner, R. S. Cotran, V. Pardo and E. R. Unanue. A monoclonal cell component in experimental immunological glomerulonephritis. J. Exp. Med. 147:369–384 (1978).Google Scholar
  17. 17.
    H. Latta and S. Fligiel. Mesangial fenestrations, sieving, filtration and flow. Lab. Invest. 52:591–598 (1985).Google Scholar
  18. 18.
    P. C. Shingal, C. Ding, S. Decandido, N. Franki, R. M. Hays and D. Schlondorff. Endocytosis by cultured mesangial cells and associated changes in prostaglandin E2 synthesis. Am. J. Physiol. 252:627–634 (1987).Google Scholar
  19. 19.
    C. Cuvier, L. Roblot-Treupel, S. Chevillard, J. M. Millot, M. Manfait, G. Bastian, P. Couvreur and M. F. Poupon. Doxorubicin-loaded nanospheres bypass tumour cell multidrug resistance. Biochim. Pharmacol. 44:509–517 (1992).Google Scholar
  20. 20.
    P. Couvreur, L. Roblot-Treupel, M. F. Poupon, F. Brasseur and F. Puisieux. Nanoparticles as microcarriers for anticancer drugs. Adv. Drug Deliv. Rev. 5:209–230 (1990).Google Scholar
  21. 21.
    N. Chianniekulchai, N. Ammoury, B. Caillou, J. P. Devissaguet and P. Couvreur. Hepatic tissue distribution of doxorubicin-loaded nanoparticles after i.v. administration in reticulosarcoma M5076 metastases-bearing mice. Cancer Chemother. Pharmacol. 26:122–126 (1990).Google Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Luc Manil
    • 1
  • Jean-Claude Davin
    • 1
  • Charles Duchenne
    • 1
  • Christine Kubiak
    • 2
  • Jacqueline Foidart
    • 1
  • Patrick Couvreur
    • 2
  • Philippe Mahieu
    • 1
  1. 1.Internal Medicine DepartmentUniversity of LIEGELiègeBelgium
  2. 2.Laboratoire de Pharmacie Galénique et de BiopharmacieUniversité de PARIS-SudChatenay-MalabryFrance

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