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.
OBJECTIVE
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 1,000 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 1,000 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.
Illum
L
L
Institute of Pharmaceutical Sciences, University of Nottingham, University Park, UK. lisbeth_illum@westpharma.com
Church
A E
AE
Butterworth
M D
MD
Arien
A
A
Whetstone
J
J
Davis
S S
SS
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003102:Colloids; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics; D003911:Dextrans; D005079:Excipients; D007501:Iron / Q000737:chemistry / Q000493:pharmacokinetics; D007504:Iron Radioisotopes; D008198:Lymph Nodes / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012821:Silanes; D013499:Surface Properties; D014018:Tissue Distribution
D003102:Colloids; D003287:Contrast Media; D003911:Dextrans; D005079:Excipients; D007504:Iron Radioisotopes; D012821:Silanes; C052889:alpha, omega-dicarboxymethylpoly(oxyethylene)-magnetite; D011092:Polyethylene Glycols; D007501:Iron; C071717:trimethoxysilane