Abstract
Purpose. Nanoparticles can be utilised for targeting drugs to the regional lymph nodes or as diagnostic agents. The surface modification of magnetite nanospheres with poly(ethylene glycol) (PEG) has been assessed by in vitro characterisation and in vivo studies following subcutaneous administration to the rat.
Methods. Magnetite nanospheres were prepared with a grafted PEG layer using various PEG lengths from 350 to 1000 Da. Thermogravimetric analysis was utilised to measure the adsorbed amount of PEG. Colloid stability was confirmed by measurement of the particle size and electrophoretic mobility. The kinetics of injection site drainage and lymph node retention were determined 2 hours after subcutaneous administration, for nanospheres coated with PEG lengths of 350, 550, 750, and 1000 Da. For the 750 PEG coated nanospheres, the kinetics of distribution was determined over a 48–hour time course.
Results. The distribution of the nanospheres was modified and the lymph node localisation enhanced by altering the surface coverage of PEG on the magnetic surface.
Conclusions. PEG–coated magnetite nanospheres with different surface characteristics can be utilised to target a diagnostic agent to regional lymph nodes.
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REFERENCES
A. E. Hawley, S. S. Davis, and L. Illum. Targeting of colloids to lymph nodes: Influence of lymphatic physiology and colloidal characteristics. Adv. Drug Deliv. Rev. 17:129–148 (1995).
J. Fruhling. Lymph and lymphatic pathophysiology. In P. H. Cox (ed.), Progress In Radiopharmacology, Elsevier, Amsterdam, 1981 pp. 223–229.
A. Turner, C. Kirby, J. Senior, and G. Gregoriadis. Fate of cholesterol–rich liposomes after subcutaneous injection in rats. Biochim. Biophys. Acta 760:119–125 (1983).
S. M. Moghimi, A. E. Hawley, N. M. Christy, T. Gray, L. Illum, and S. S. Davis. Surface engineered nanospheres with enhanced drainage into lymphatics and uptake by macrophages of the regional lymph nodes. FEBS Lett. 344:25–30 (1994).
A. E. Hawley, L. Illum, and S. S. Davis. Lymph node localisation of biodegradable nanospheres surface modified with poloxamer and poloxamine block copolymers. FEBS Lett. 400:319–323 (1997).
A. E. Hawley, L. Illum, and S. S. Davis. Preparation of biodegradable, surface engineered PLGA nanospheres with enhanced lymphatic drainage and lymph node uptake. Pharm. Res. 14:657–661 (1997).
P. M. Som. Detection of metastasis in cervical lymph nodes. CT and MR criteria and differential diagnosis. Am. J. Radiol. 158: 961–969 (1992).
R. S. Molday and D. Mackenzie. Immunospecific ferromagnetic iron–dextran reagents for the labelling and magnetic separation of cells. J. Immun. Meth. 52:353–367 (1982).
M. Suzuki, M. Shinkai, M. Kamihira, and T. Kobayashi. Preparation and characteristics of magnetite–labelled antibody with the use of poly(ethylene glycol) derivatives. Biotech. Appl. Biochem. 21:335–345 (1995).
T. Mihama, T. Yoshimoto, K. Ohwada, K. Takahashi, S. Akimoto, Y. Saito, and Y. Inada. Magnetic lipase adsorbed to a magnetic fluid. J. Biotechnol. 7:141–146 (1988).
T. Yoshimoto, T. Mihama, K. Takahashi, Y. Saito, Y. Tamaura, and Y. Inada. Chemical modification of enzymes with activated magnetic modifier. Biochem. Biophys. Res. Comm. 145:908–914 (1987).
M. D. Butterworth, L. Illum, and S. S. Davis. Preparation of ultrafine silica–and PEG–coated magnetite particles. Colloids and Surfaces A: Physicochemical and Engineering Aspects 179:93–102 (2001).
R. Massart. Preparation of aqueous magnetic liquids in alkaline and acidic media. IEEE Trans. Magn. 17:1247–1248 (1981).
S. Stolnik, S. E. Dunn, M. C. Garnett, M. C. Davies, A. G. A. Coombes, D. C. Taylor, M. P. Irving, S. C. Purkiss, T. F. Tadross, S. S. Davis, and L. Illum. Surface modification of poly(lactide–co–glycolide) nanoparticles by novel biodegradable poly(lactide)–poly(ethylene glycol) copolymers. Pharm. Res. 11:1800–1808 (1994).
H. M. Patel, N. S. 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).
N. B. Argent, J. Liles, D. Rodham, C. B. Clayton, R. Wilkinson, and P. H. Bayliss. A new method for measuring the blood volume of the rat using 113m Indium as a tracer. Lab. Anim. 28:172–175 (1994).
R. K. Iler. The Chemistry of Silica, John Wiley & Sons, New York, 1979 89 p.
F. Th. Tadros and B. Vincent. Influence of temperature and electrolytes on the adsorption of poly(ethylene oxide)–poly(propylene oxide) block copolymer on polystyrene latex and the stability of the polymer–coated particles. J. Phys. Chem. 84:1575–1580 (1980).
D. D. Lasio. Novel applications of liposomes. Trends Biotechnol. 16:307–321 (1998).
C. Oussoren and G. Storm. Lymphatic uptake and biodistribution of liposomes after subcutaneous injection: III. Influence of surface modification with poly(ethylene glycol). Pharm. Res. 14:1479–1484 (1997).
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Illum, L., Church, A.E., Butterworth, M.D. et al. Development of Systems for Targeting the Regional Lymph Nodes for Diagnostic Imaging: In Vivo Behaviour of Colloidal PEG-Coated Magnetite Nanospheres in the Rat Following Interstitial Administration. Pharm Res 18, 640–645 (2001). https://doi.org/10.1023/A:1011081210142
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DOI: https://doi.org/10.1023/A:1011081210142