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Preparation of Sterically Stabilized Human Serum Albumin Nanospheres Using a Novel Dextranox-MPEG Crosslinking Agent

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Abstract

Human serum albumin (HSA) nanospheres with a size less than 200 nm in diameter were prepared using a modified coacervation method and crosslinking with methyl polyethylene glycol modified oxidized Dextram (Dextranox-MPEG) which created a sterically stabilizing polyethylene oxide surface layer surrounding the nanospheres. The crosslinking efficiency and the surface characteristics of glutaraldehyde and Dextranox-MPEG crosslinked HSA nanospheres were determined and compared. The zeta potential of the Dextranox-MPEG crosslinked particles was significantly lower than that of glutaraldehyde stabilized particles. The existence of a hydrated steric barrier surrounding the nanospheres was confirmed by an electrolyte and pH induced flocculation test. The Dextranox-MPEG crosslinked nanospheres showed a significantly reduced plasma protein adsorption on the particle surface compared with glutaraldehyde crosslinked nanospheres.

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REFERENCES

  1. S.S. Davis and L. Illum. Colloidal delivery systems, opportunities and challenges. In E. Tomlinson and S.S. Davis (eds.), Site-Specific Drug Delivery: Cell Biology, Medical and Pharmaceutical Aspects, John Wiley & Sons, Chichester, 1986, pp. 931–933.

    Google Scholar 

  2. L. Illum and S.S. Davis. The kinetics of uptake and organ deposition of colloidal drug carrier particles delivered to rabbits. In Proceedings of Second European Congress on Biopharmaceuticals and Pharmacokinetics, Salamanca, Spain, Vol. II, Technique et Documentation, Paris, 1984, pp.97-105.

    Google Scholar 

  3. S.M. Moghimi, C.J.H. Porter, I.S. Muir, L. Illum and S.S. Davis. Non-phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particle size and hydrophilic coating: Biochem. Biophys. Res. Commun. 127: 861–866 (1991).

    Google Scholar 

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

    Google Scholar 

  5. L. Illum, S.S. Davis, C.G. Wilson, N.W. Thomas, M. Frier and J.G. Hardy. Blood clearance and organ deposition of intravenously administered colloidal particles: the effects of particle size, nature and shape. Int. J. Pharm. 12: 135–139 (1982).

    Google Scholar 

  6. P. Artursson. The fate of microparticulate drug carriers after intravenous administration. In L. Illum and S.S. Davis (eds.), Polymers in Controlled Drug Delivery, Wright, Bristol. 1987, pp. 15–24.

    Google Scholar 

  7. S.M. Moghimi, H. Hedeman, I.S. Muir, L. Illum and S.S. Davis. An investigation of the filtration capacity and the fate of large filtered sterically stabilized microspheres in rat spleen. Biochim. Biophys. Acta 1157: 233–240 (1993).

    Google Scholar 

  8. S. Bogdansky. Natural Polymers as Drug Delivery Systems. In M. Casin and R. Langer. (eds.), Biodegradable Polymers as Drug Delivery Systems, Marcel, Dekker, 1990, pp. 240–246.

    Google Scholar 

  9. R. Arshady. Albumin microspheres and microcapsules: methodology of manufacturing techniques. J. Controlled Release. 14: 111–131 (1990).

    Google Scholar 

  10. W. Lin, A.G.A. Coombes, M.C. Davies, S.S. Davis and L. Illum. Preparation of sub 100 nm human serum albumin nanospheres using a pH-coacervation method. J. Drug Targeting 1:237–243 (1993).

    Google Scholar 

  11. Y. Chen, N. Willmott and A.T. Florence. The in vitro degradation of protein microspheres by trypsin. J. Pharm. Pharmacol. 39:36p (1987).

    Google Scholar 

  12. O. Pruksananonda. Investigation of crosslinking in albumin microspheres. PhD thesis, University of North Carolina, USA, 1989, pp. 69–72.

  13. R.C. Oppenhein, Gelatin microspheres as drug carrier systems. In L. Illum and S.S. Davis. (eds.), Polymers in Control Drug Delivery, Wright, Bristol, 1987, pp. 73–86.

    Google Scholar 

  14. G. Chen, W. Lin, A. Coombes, S.S. Davis and L. Illum. Preparation of human serum albumin microspheres by a novel acetone-heat denaturation method. J. Microencapsulation (1993) 4: 395–407 (1994).

    Google Scholar 

  15. K. Peters and F.M. Richards. Chemical crosslinking: reagent and problems in studies of membrane structure. Ann. Rev. Biochem. 46: 523–551 (1977).

    Google Scholar 

  16. S.S. Davis, S.N. Mills and E. Tomlinson. Chemically crosslinked albumin microspheres for the controlled release of incorporated rose bengal after intramuscular injection into rabbits. J. Controlled Release 4: 293–302 (1987).

    Google Scholar 

  17. A.T. Florence and D. Attwood. Physicochemical principles of pharmacy, Macmillan Press, London, 2nd ed. 1988, pp. 229–278.

    Google Scholar 

  18. S.M. Moghimi and H.M. Patel. Tissue specific opsonins for phagocytic cells and their different affinity for cholesterol-rich liposomes. FEBS lett. 233: 143–147 (1988).

    Google Scholar 

  19. 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 dysoponins in the serum. Biochim. Biophys. Acta 1179: 157–165 (1993).

    Google Scholar 

  20. M.E. Norman, P. Williams and L. Illum. Human serum albumin as a probe for surface conditioning (opsonization) of block co-polymer coated microspheres. Biomaterials 13:841–849 (1992).

    Google Scholar 

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Lin, W., Coombes, A.G.A., Garnett, M.C. et al. Preparation of Sterically Stabilized Human Serum Albumin Nanospheres Using a Novel Dextranox-MPEG Crosslinking Agent. Pharm Res 11, 1588–1592 (1994). https://doi.org/10.1023/A:1018957704209

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