Skip to main content
SpringerLink
Log in

Surface Modification of Poly(lactide-co-glycolide) Nanospheres by Biodegradable Poly(lactide)-Poly(ethylene glycol) Copolymers

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

The modification of surface properties of biodegradable poly(lactide-co-glycolide) (PLGA) and model polystyrene nanospheres by poly(lactide)-poly(ethlene glycol) (PLA:PEG) copolymers has been assessed using a range of in vitro characterization methods followed by in vivo studies of the nanospheres biodistribution after intravenous injection into rats. Coating polymers with PLA:PEG ratio of 2:5 and 3:4 (PEG chains of 5000 and 2000 Da, respectively) were studied. The results reveal the formation of a PLA: PEG coating layer on the particle surface resulting in an increase in the surface hydrophilicity and decrease in the surface charge of the nanospheres. The effects of addition of electrolyte and changes in pH on stability of the nanosphere dispersions confirm that uncoated particles are electrostatically stabilized, while in the presence of the copolymers, steric repulsions are responsible for the stability. The PLA:PEG coating also prevented albumin adsorption onto the colloid surface. The evidence that this effect was observed for the PLA:PEG 3:4 coated nanospheres may indicate that a poly(ethylene glycol) chain of 2000 Da can provide an effective repulsive barrier to albumin adsorption. The in vivo results reveal that coating of PLGA nanospheres with PLA:PEG copolymers can alter the biodistribution in comparison to uncoated PLGA nanospheres. Coating of the model polystyrene nanospheres with PLA:PEG copolymers resulted in an initial high circulation level, but after 3 hours the organ deposition data showed values similar to uncoated polystyrene spheres. The difference in the biological behaviour of coated PLGA and polystyrene nanospheres may suggest a different stability of the adsorbed layers on these two systems. A similar biodistribution pattern of PLA:PEG 3:4 to PEG 2:5 coated particles may indicate that poly(ethylene glycol) chains in the range of 2000 to 5000 can produce a comparable effect on in vivo behaviour.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. L. Illum and S. S. Davis. The organ uptake of intravenously administered colloidal particles can be altered using nonionic surfactant (poloxamer 338), FEBS Lett. 167:70–82 (1984).

    Google Scholar 

  2. J. Senior, C. Delgado, D. Fisher, C. Tilcock and G. Gregoriadis. Influence of surface hydrophilicity of liposomes on their interaction with plasma protein and clearance from the circulation: studies with poly(ethylene glycol)-coated vesicles. Biochim. Biophys. Acta, 1062:77–82 (1991).

    Google Scholar 

  3. R. H. Muller, K. H. Walis, S. D. Troster, and J. Kreuter. In vitro characterization of poly(methyl-methacrylate) nanospheres and correlation to their in vivo fate. J. Control. Rel. 20:237–246 (1992).

    Google Scholar 

  4. L. Illum, S. S. Davis, R. H. Muller, E. Mak and P. West. The organ distribution and circulation time of intravenously injected colloidal carriers sterically stabilised with block-copolymer-poloxamine 908. Life Sci. 40:367–374 (1987).

    Google Scholar 

  5. S. M. Moghimi, L. Illum and S. S. Davis. Organ specific targeting of synthetic and natural drug carriers. In: B. R. Jetter (ed.) Homing Mechanisms and Cellular Targeting, Advances in Molecular and Cell Biology, Vol. 9, pp 263–282

  6. I. S. Muir, S. M. Moghimi, L. Illum, S. S. Davis and M. C. Davies. The effect of block copolymeres on the uptake of model microspheres by Kupffer cells—in vitro and in vivo studies. Biochem. Soc. Trans. 19:329S (1991).

    Google Scholar 

  7. C. J. Porter, S. M. Moghimi, L. Illum. and S. S. Davis. The polyoxyethylene/polyoxypropylene block co-polymer Poloxamer-407 selectively redirects intravenously injected microspheres to sinusoidal endothelial cells of rabbit bone marrow. FEBS 305:62–66 (1992).

    Google Scholar 

  8. S. M. Moghimi, I. S. Muir, L. Illum, S. S. Davis, and V. Kolb-Bachofen. Coating particles with a block co-polymer (poloxamine 908) supress opsonization but permits the activity of dysopsonins in the serum. Biochim. Biophys. Acta. 1179:157–165 (1993)

    Google Scholar 

  9. J. B. Kayes and D. A. Rawlins. Adsorption characteristics of certain polyoxethylene-polyoxypropylene block co-polymers on polystyrene latex. Coll. Polym. Sci. 257:622–629 (1979).

    Google Scholar 

  10. L. Illum, L. O. Jacobsen, R. H. Muller, E. Mak and S. S. Davis. Surface characteristics and the interaction of colloidal particles with mouse peritoneal macrophages. Biomaterials 8:113–117 (1987).

    Google Scholar 

  11. L. Illum, P. West, C. Washington, and S. S. Davis. The effect of stabilizing agents on the organ distribution of lipid emulsions. Int. J. Pharm. 54:41–49 (1989).

    Google Scholar 

  12. J. H. Senior. Fate and behaviour of liposomes in vivo: A review of controlling factors. Crit. Rev. Ther. Drug Carrier. Syst. 3: 123–193 (1987).

    Google Scholar 

  13. S. M. Moghimi, C. J. H. Porter, L. Illum, and S. S. Davis. The effect of poloxamer-407 on liposome stability and targeting to bone marrow: comparison with polystyrene microspheres. Int. J. Pharm. 68:121–126 (1991).

    Google Scholar 

  14. A. L. Klibanov, K. Maruyama, V. P. Torcelini, and L. Huang. Activity of amphipathic poly(ethylene glycol) 5000 to prolong the circulation time of liposomes depends on the liposome size and is unfavorable for immunoliposome binding target. FEBS Lett. 268:235–237 (1990).

    Google Scholar 

  15. M. C. Woodle and D. D. Lasic. Sterically stabilized liposomes. Biochem. Biophys. Acta 1113:171–191 (1992).

    Google Scholar 

  16. J. R. Churchill and F. G. Hutchinson. Biodegradable amphipathic copolymers. European Patent Application, 0 092 918, 1983.

  17. J. R. Churchill and F. G. Hutchinson. Biodegradable amphipathic copolymers. European Patent Application 0 166 596, 1986.

  18. G. Spenlehauer, M. Veillard and T. Nerrechia. Pharmaceutical microspheres containing biocompatible and biodegradable surfactants and polymers. PCT Int. Appl. WO 91 15, 193, 1991.

    Google Scholar 

  19. R. Gref, Y. Minamitake, M. T. Perachchia, V. Trubetskoy, A. Milshteyn, J. Sinkule, V. Torchilin and R. Langer. Biodegradable PEG-coated stealth nanospheres. Proceed. Intern. Symp. Control. Rel. Bioact. Mater. 20:131–132 (1993).

    Google Scholar 

  20. S. Stolnik, M. C. Davies, L. Illum, S. S. Davis, M. Bousta and M. Vert. J. Control. Rel. 30:57–67 (1994).

    Google Scholar 

  21. S. J. Douglas, L. Illum, S. S. Davis and J. Kreuter. Particle size and size distribution of poly(butyl-2-cyanoacrylate) nanoparticles. J. Colloid and Interface Sci. 101:149–158 (1984).

    Google Scholar 

  22. H. Z. Cummins and E. R. Pike (eds.) Photon Correlation and Light Beating Spectroscopy, NATO-ASI Series, Plenum Press, New York, 1974.

    Google Scholar 

  23. L. Illum, S. S. Davis, R. H. Muller, E. Mak, and P. West. The organ distribution and circulation time of intravenously injected colloidal carriers sterically stabilised with block-copolymer-poloxamine 908. Life Sci. 40:1553–1560 (1987).

    Google Scholar 

  24. P. D. Scholes, M. C. Davies, L. Illum and S. S. Davis. Radiolabelling of biodegradable microspheres for site specific drug delivery. Proceed. Inter. Symp. Control. Rel. Bioact. Mat. 19:154–155 (1992).

    Google Scholar 

  25. Y. Huh, W. Donaldson and F. J. Johnson. A radiation induced bonding of iodine at the surface of uniform polystyrene particles. Radiation Research 60:42–53 (1974).

    Google Scholar 

  26. H. M. Patel, S. N. Tuzel and B. E. Ryman. Inhibitory effect of cholesterol on the uptake of liposomes by liver and spleen. Biochim. Biophys. Acta. 761:142–151 (1983).

    Google Scholar 

  27. C. G. Golander, J. N. Herron, K. Lim, P. Claesson, P. Stenius and J. D. Andrade. Properties of immobilized PEG films and interacton with proteins: I Experiments and modeling. In J. M. Harris (ed.) Poly(ethylene Glycol) Chemistry: Biotechnical and Biomedical Applications, Plenum Press, 1992, pp. 221–245.

  28. W. R. Gombotz, W. Guanghui, T. A. Horbert and A. S. Hoffman, Protein adsorption to and elution from polyether surfaces. In: J. M. Harris (ed.), Poly(ethylene Glycol) Chemistry: Biotechnical and Biomedical Applications, Plenum Press, New York, 1992, pp. 249–261.

    Google Scholar 

  29. M. E. Norman, P. Williams and L. Illum. Influence of block copolymers on the adsorption of plasma proteins to microspheres. Biomaterials 14:193–202 (1993).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Nottingham University, University Park, Nottingham, NG7 2RD, U.K

    Snjezana Stolnik, Susan E. Dunn, Martin C. Garnett, Martyn C. Davies, Allan G. A. Coombes, Stanley S. Davis & Lisbeth Illum

  2. Zeneca Agrochemicals, Jealott’s Hill, Brakwell, U.K

    D. C. Taylor, M. P. Irving & S. C. Purkiss

  3. Zeneca Pharmaceuticals, Alderley Park, Macclesfield, U.K

    T. F. Tadros

Authors
  1. Snjezana Stolnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan E. Dunn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin C. Garnett
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martyn C. Davies
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Allan G. A. Coombes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. C. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. P. Irving
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. C. Purkiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. T. F. Tadros
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Stanley S. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Lisbeth Illum
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stolnik, S., Dunn, S.E., Garnett, M.C. et al. Surface Modification of Poly(lactide-co-glycolide) Nanospheres by Biodegradable Poly(lactide)-Poly(ethylene glycol) Copolymers. Pharm Res 11, 1800–1808 (1994). https://doi.org/10.1023/A:1018931820564

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018931820564

Search

Navigation