Advertisement

Pharmaceutical Research

, Volume 17, Issue 10, pp 1250–1258 | Cite as

Niosomes and Polymeric Chitosan Based Vesicles Bearing Transferrin and Glucose Ligands for Drug Targeting

  • Christine Dufes
  • Andreas G. Schätzlein
  • Laurence Tetley
  • Alexander I. Gray
  • Dave G. Watson
  • Jean-Christophe Olivier
  • William Couet
  • Ijeoma F. Uchegbu
Article

Abstract

Purpose. To prepare polymeric vesicles and niosomes bearing glucose or transferrin ligands for drug targeting.

Methods. A glucose-palmitoyl glycol chitosan (PGC) conjugate was synthesised and glucose-PGC polymeric vesicles prepared by sonication of glucose-PGC/ cholesterol. N-palmitoylglucosamine (NPG) was synthesised and NPG niosomes also prepared by sonication of NPG/ sorbitan monostearate/ cholesterol/ cholesteryl poly-24-oxyethylene ether. These 2 glucose vesicles were incubated with colloidal concanavalin A gold (Con-A gold), washed and visualised by transmission electron microscopy (TEM). Transferrin was also conjugated to the surface of PGC vesicles and the uptake of these vesicles investigated in the A431 cell line (over expressing the transferrin receptor) by fluorescent activated cell sorter analysis.

Results. TEM imaging confirmed the presence of glucose units on the surface of PGC polymeric vesicles and NPG niosomes. Transferrin was coupled to PGC vesicles at a level of 0.60 ± 0.18 g of transferrin per g polymer. The proportion of FITC-dextran positive A431 cells was 42% (FITC-dextran solution), 74% (plain vesicles) and 90% (transferrin vesicles).

Conclusions. Glucose and transferrin bearing chitosan based vesicles and glucose niosomes have been prepared. Glucose bearing vesicles bind Con-A to their surface. Chitosan based vesicles are taken up by A431 cells and transferrin enhances this uptake.

polymeric vesicles glucose vesicles transferrin vesicles 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

REFERENCES

  1. 1.
    M. Ogris, S. Brunner, S. Schuller, R. Kircheis, and E. Wagner. PEGylated DNA/transferrin-PEI complexes: Reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther. 6:595–605 (1999).Google Scholar
  2. 2.
    R. Polt, F. Porreca, L. Z. Szabo, E. J. Bilsky, P. Davis, T. J. Abbruscato, T. P. Davis, R. Horvath, H. I. Yamamura, and V. J. Hruby. Glycopeptide enkephalin analogs produce analgesia in mice–Evidence for penetration of the blood-brain-barrier. Proc. Natl. Acad. Sci. USA 91:7114–7118 (1994).Google Scholar
  3. 3.
    R. I. Mahato, S. Takemura, K. Akamatsu, M. Nishikawa, Y. Takakura, and M. Hashida. Physicochemical and disposition characteristics of antisense oligonucleotides complexed with glycosylated poly(L-lysine). Biochem. Pharmacol. 53:887–895 (1997).Google Scholar
  4. 4.
    I. F. Uchegbu, A. G. Schatzlein, L. Tetley, A. I. Gray, J. Sludden, S. Siddique, and E. Mosha. Polymeric chitosan-based vesicles for drug delivery. J. Pharm. Pharmacol. 50:453–458 (1998).Google Scholar
  5. 5.
    D. Papahadjopoulos, T. M. Allen, A. Gabizon, E. Mayhew, K. Matthay, S. K. Huang, K. D. Lee, M. C. Woodle, D. D. Lasic, and C. Redemann. Sterically stabilized liposomes: Improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc. Natl. Acad. Sci. USA 88:11460–11464 (1991).Google Scholar
  6. 6.
    F. Yuan, M. Leunig, S. K. Huang, D. A. Berk, D. Papahadjopoulos, and R. K. Jain. Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. Cancer Res. 54:3352–3356 (1994).Google Scholar
  7. 7.
    I. F. Uchegbu, J. A. Double, J. A. Turton, and A. T. Florence. Distribution, metabolism and tumoricidal activity of doxorubicin administered in sorbitan monostearate (Span 60) niosomes in the mouse. Pharm. Res. 12:1019–1024 (1995).Google Scholar
  8. 8.
    Y. K. Song and D. X. Liu. Free liposomes enhance the transfection activity of DNA/lipid complexes in vivo by intravenous administration. Biochim. Biophys. Acta 1372:141–150 (1998).Google Scholar
  9. 9.
    L. G. Barron, L. Gagne, and F. C. Szoka, Jr. Lipoplex-mediated gene delivery to the lung occurs within 60 minutes of intravenous administration. Human Gene Ther. 10:1683–1694 (1999).Google Scholar
  10. 10.
    R. D. Broadwell, B. J. Baker-Cairns, P. M. Friden, C. Oliver, and J. C. Villegas. Transcytosis of protein through the mammalian cerebral epithelium and endothelium. III. Receptor-mediated transcytosis through the blood-brain barrier of blood-borne transferrin and antibody against the transferrin receptor. Experimental Neurol. 142:47–65 (1996).Google Scholar
  11. 11.
    C. L. Farrell and W. M. Pardridge. Blood-brain-barrier glucose transporter is asymmetrically distributed on brain capillary endothelial lumenal and ablumenal membranes–An electron-microscopic immunogold study. Proc. Natl. Acad. Sci. USA 88: 5779–5783 (1991).Google Scholar
  12. 12.
    W. M. Pardridge. Molecular regulation of blood-brain barrier GLUT1 glucose transporter. In J. Greenwood, D. J. Begley and M. B. Segal (eds.), New Concepts of a blood brain barrier, Plenum Press, New York, 1995, pp. 81–88.Google Scholar
  13. 13.
    T. Higashi, N. Tamaki, T. Honda, T. Torizuka, T. Kimura, T. Inokuma, G. Ohshio, R. Hosotani, M. Imamura, and J. Konishi. Expression of glucose transporters in human pancreatic tumors compared with increased FDG accumulation in PET study. J. Nucl. Med. 38:1337–1344 (1997).Google Scholar
  14. 14.
    T. A. D. Smith. Facilitative glucose transporter expression in human cancer tissue. Br. J. Biomed. Sci. 56:285–292 (1999).Google Scholar
  15. 15.
    I. F. Uchegbu. The biodistribution of novel 200nm palmitoyl muramic acid vesicles. Int. J. Pharm. 162:19–27 (1998).Google Scholar
  16. 16.
    Y. Lapidot, N. D. Groot, and I. Fry-Shafrir. II A general method for the preparation of acylaminoacyl-tRNA. Biochim. Biophys. Acta 145:292–299 (1967).Google Scholar
  17. 17.
    C. R. McBroom, C. H. Samanen, and I. J. Goldstein. Carbohydrate antigens: Coupling of carbohydrates to proteins by diazonium and phenylisothiocyanate reaction. Meth. Enzymol. 28:212–219 (1972).Google Scholar
  18. 18.
    M. Monsigny, A. C. Roche, and P. Midoux. Uptake of neoglycoproteins via membrane lectins of L1210 cells evidenced by quantitative flow cytofluorometry and drug targeting. Biol. Cell 51: 187–196 (1984).Google Scholar
  19. 19.
    N. Benhamou and G. B. Ouellette. Ultrastructural-localization of glycoconjugates in the fungus ascocalyx-abietina, the scleroderris canker agent of conifers, using lectin gold complexes. J. Histochem. Cytochem. 34:855–867 (1986).Google Scholar
  20. 20.
    G. E. Davies and G. R. Stark. Use of dimethyl suberimidate, a cross-linking agent in studying the subunit structure of oligomeric proteins. Proc. Natl. Acad. Sci. USA 66:651–656 (1970).Google Scholar
  21. 21.
    J. C. Stavridis, G. Deliconstantinos, M. C. Psallidopoulos, N. A. Armenakas, D. J. Hadjiminas, and J. Hadjiminas. Construction of transferrin-coated liposomes for in vivo transport of exogenous DNA to bone marrow erythroblasts in rabbits. Exp. Cell Res. 164:568–572 (1986).Google Scholar
  22. 22.
    O. H. Lowry, N. J. Rosenburgh, A. L. Farr, and R. J. Randall. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193:265–275 (1951).Google Scholar
  23. 23.
    T. Hoshino, M. Misaki, M. Yamamoto, H. Shimizu, Y. Ogawa, and H. Toguchi. In-vitro cytotoxicities and in-vivo distribution of transferrin platinum(Ii) complex. J. Pharm. Sci. 84:216–221 (1995).Google Scholar
  24. 24.
    T. Hoshino, M. Misaki, M. Yamamoto, H. Shimizu, Y. Ogawa, and H. Toguchi. Receptor-binding, in-vitro cytotoxicity, and in-vivo distribution of transferrin-bound cis-platinum(Ii) of differing molar ratios. J. Control. Rel. 37:75–81 (1995).Google Scholar
  25. 25.
    R. Hori and Y. Ikegami. Studies on carbohydrate derivatives V. Synthesis of alkyl galactosides and alkyl glucosides. Yakugaku Zasshi 79:80–83 (1951).Google Scholar
  26. 26.
    G. Vanlerberghe and J. L. Morancais. Niosomes in perspective, STP. Pharma Sci. 6: 5–11 (1996).Google Scholar
  27. 27.
    H. Kiwada, H. Niimura, Y. Fujisaki, S. Yamada, and Y. Kato. Application of synthetic alkyl glycoside vesicles as drug carriers. I Preparation and physical properties. Chem. Pharm. Bull. 33: 753–759 (1985).Google Scholar
  28. 28.
    I. F. Uchegbu and A. T. Florence. Non-ionic surfactant vesicles (niosomes): Physical and pharmaceutical chemistry, some aspects of the niosomal delivery of doxorubicin. Adv. Coll. Interf. Sci. 58:1–55 (1995).Google Scholar
  29. 29.
    W. M. Pardridge, R. J. Boado, and C. R. Farrell. Brain-type glucose transporter (Glut-1) is selectively localized to the bloodbrain-barrier–Studies with quantitative western blotting and in situ hybridization. J. Biol. Chem. 265:18035–18040 (1990).Google Scholar
  30. 30.
    A. A. Phylchenkov, I. I. Slukvin, Y. I. Kudryavets, L. P. Didkovskaya, G. A. Kulik, V. P. Chernishov, and A. I. Bykorez. Expression and functional-activity of transferrin receptor in human tumor-cell of different histogenesis. Eksperimental. Onkol. 14:22–27 (1992).Google Scholar

Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Christine Dufes
    • 1
    • 2
  • Andreas G. Schätzlein
    • 3
  • Laurence Tetley
    • 4
  • Alexander I. Gray
    • 1
  • Dave G. Watson
    • 1
  • Jean-Christophe Olivier
    • 2
  • William Couet
    • 2
  • Ijeoma F. Uchegbu
    • 5
  1. 1.Department of Pharmaceutical SciencesUniversity of Strathclyde, Strathclyde Institute for Biomedical SciencesGlasgowUnited Kingdom
  2. 2.Faculté de Médecine et PharmacieLaboratoire de Pharmacie Galénique et BiopharmaciePoitiersFrance
  3. 3.Department of Medical OncologyUniversity of Glasgow, Garscube EstateGlasgowUnited Kingdom
  4. 4.Institute of Biomedical and Life SciencesUniversity of GlasgowGlasgowUnited Kingdom
  5. 5.Department of Pharmaceutical SciencesUniversity of Strathclyde, Strathclyde Institute for Biomedical SciencesGlasgowUnited Kingdom

Personalised recommendations