Abstract
Magnetically responsive gelatin microspheres for the targeting of drugs have been prepared using a water-in-oil emulsion technique with chemical cross-linking of the protein. The manufacturing variables affecting microsphere size, size distribution and surface characteristics have been examined as well as the magnetic responsivenessin vitro.
Sesame oil was utilized for non-aqueous phase and magnetic gelatin microspheres of different size from 1.89 to 14.88 μm in mean diameter could be obtained with variation of HLB values of non-ionic surfactants. The content of magnetite which uniformly distributed throughout the microspheres was 26.7% (w/w). It was possible to control the localization of magnetic gelatin microspheres at specific sites within capillary models by using external magnetic field of under 5K gauss.
Similar content being viewed by others
Literature Cited
Goldberg, E.P.: “Targeted Drugs”, John Wiley & Sons, New York, p. 296 (1983).
Gregoriadis, G., Senior, D. and Trouet, A.: “Targeting of Drugs”, Plenum Press, New York, p. 419 (1982).
Schacht, E., Ruys, Vermeersch, J., Remon, J.P. and Duncan, R.: Use of polysaccharides as drug carriers.Annals. N.Y. Acad. Sci.,446, 199 (1985).
Bodor, N.: Targeting of drugs to the brain, in “Drug and Enzyme Targeting” (Widder, K. J. and Green R. ed), Academic Press, London, p. 381 (1985).
Gregoriadis, G. and Allison, A.C. “Liposomes in biological systems”, John Wiley & Sons, New York, p. 412 (1980).
Davis, S.S. and Illum, L.: The targeting of drugs using polymeric microspheres.British Polymer J.,15, 160 (1983).
Oppenheim, R.C.: Solid colloidal drug delivery systems.Int. J. Pharm.,8, 217 (1981).
Gregoriadis, G.: “Drug Carriers in Biology and Medicine”, Academic Press, London, p. 363 (1981).
Widder, K.J. and Senyei, A.E.: Magnetic microspheres: A vehicle for selective targeting drugs.Pharmac. Ther.,20, 377 (1983).
Morimoto, Y., Okumua, M., Sugibayashi, K. and Kato, Y.: Biomedical applications of magnetic fluids. II. Preparation and magnetic guidance of magnetic albumin microsphere for site specific drug deliveryin vivo.J. Pharm. Dyn.,4, 624 (1981).
Tanaka, T., Takino, S. and Utsumi, I.: A new gelatinized sustained-release dosage form.J. Pharm. Sci.,52, 664 (1963).
Scheffel, U., Rhodes, B.A., Natarajan, T.K. and Wagner, Jr., N.N.: Albumin microspheres for study of the reticuloendothelial system.J. Nucl. Med.,13, 498 (1972).
Oppenheim, R.C.: Nanoparticles, in “Drug Delivery System” (Juliano, R.L. ed.), Oxford Univer. Press, Oxford, pp. 177 (1980).
Sezaki, H., Hashida, M. and Muranishi, S.: Gelatin microspheres as carriers for antineoplastic agents, in “Optimization of Drug Delivery” (Bundgaard, H., Hansen, A.B. and Kofod, H. eds.), Munksgaard, Copenhagen, pp. 316 (1982).
Morimoto, Y.: Personal communication.
Jizomoto, H.: Phase separation induced in gelatin-base coacervation systems by addition of water-soluble nonionic polymers I: Microencapsulation.J. Pharm. Sci.,73, 879 (1984).
Kramer, P.A.: Albumin microspheres as vehicles for achiving specificity in drug delivery.J. Pharm. Sci.,63, 1646 (1974).
Gallo, J.M., Hung, C.T. and Perrier, D.G.,: Analysis of albumin microsphere preparation.Int. J. Pharm.,22, 63 (1984).
Dunn, A.S.: Effects of the choice of emulsifier in emulsion polymerization, in “Emulsion Polymerization” (Piirma, I. ed.), Academic Press, New York, pp 221 (1982).
Marty, J.J., Oppenheim, R.C. and Speiser, P.: Nanoparticles-a new colloidal drug delivery system.Pharm. Acta Helv.,53, 17 (1978).
Ycshioka, T., Hashida, M., Muranishi, S. and Sezaki, H.: Specific delivery of Mitomycin C to the liver, spleen and lung: Nano and microspherical carriers of gelatin.Int. J. Pharm.,8, 131 (1981).
Eberth, K. and Merry, J.: A comparative study of emulsions prepared by ultrasound and by a conventional method. Droplet size measurements by means of a coulter counter and microscopy.Int. J. Pharm.,14, 349 (1983).
Tomlinson, E.: Microsphere delivery systems for drug targeting and controlled release.Int. J. Pharm. Technol. Prod. Manuf.,4, 49 (1983).
Oppenheim, R.C.: Solid colloidal drug delivery systems.Int. J. Pharm.,8, 217 (1981).
Willmott, N., Cummings, J., Stuart, J.F.B. and Florence, A.T.: Adriamycin-loaded albumin microspheres: Preparation,in vivo distribution and release in the rat.Biopharm. & Drug Disposition,6, 91 (1985).
McMullen, J.N., Newton, D.W. and Becker, C.H.: Pectin-gelatin complex coacervates II: Effect of microencapsulated sulfamerzine on size, morphology, recovery, and extraction of water-dispersible microglobules.J. Pharm. Sci.,73, 1799 (1984).
Illum, L. and Davis, S.S.: Effect of the nonionic surfactant poloxamer 338 on the fate and deposition of polystyrene microspheres following intravenous administration.J. Pharm. Sci. 72, 1086 (1983).
Ghose, T., Blair, A.H., Uadia, P., Kulkarni, P.N., Goundalkar, A., Mezei, M. and Ferrone, S.: Antibodies as carriers of cancer chemotherapeutic agents.Annals N.Y. Acad. Sci.,446, 213 (1985).
Treleaven, J.G., Gibson, F.M., Ugelstad, J., Rembaum, A., Philip, T., Caine, G.D. and Kemshead, J.T.: Removal of neuroblastoma cells from bone marrow with monoclonal antibodies conjugated to magnetic microspheres.The Lancet, Jan.14, 70 (1984).
Whitmore, R.L.: “Rheology of the circulation”, Pergamon Press, Oxford, (1968).
Allen, T., “Particle size measurements”, 3rd edn., Chapman and Hall, London, p. 127 (1981).
Kato, T.: Encapsulated drugs in targeted cancer therapy. in “Controlled Drug Delivery” Vol. II (Bruck, S.D. ed.), CRC Press, Boca Raton, pp. 189 (1983).
Fujimoto, S., Miyazaki, M., Enndoh, F., Takahasi, O., Shrestha, R.D., Okui, K., Morimoto, Y. and Terao, K.: Effects of intra-arterially infused biodegradable microspheres containing Mitomycin C.Cancer,55, 522 (1985).
Ratcliffe, J.H., Hunneyball, I.M., Smith, A., Wilson, C.G. and Davis, S.S.: Preparation and evaluation of biodegradable polymeric systems for the intra-articulr deliverry of drugs.J. Pharm. Pharmacol.,36, 431 (1984).
Widder, K.J., Senyei, A.E., Ovadiaa, H. and Paterson, P.Y.: Specific cell binding using Staphylococcal Protein A magnetic microspheres.J. Pharm. Sci.,70, 387 (1981).
Burgess, D.J. and Carless, J.E.: Manufacture of gelatin/gelatin coacervate microcapsules.Int. J. Pharm.,27, 61 (1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lee, K.C., Koh, I.B. & Oh, I.J. Preparation of magnetic gelatin microspheres for the targeting of drugs. Arch. Pharm. Res. 9, 145–152 (1986). https://doi.org/10.1007/BF02899998
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02899998